Molecular final just questions and fill in the blank and Molecular Biology last materials

The ______________________________ is where DNA duplication begins...there are many of these along eukaryotic chromosomes.

replication origin

________ is a tumor suppressor that can malfunction in many cancers

P53 is a tumor suppressor that can malfunction in many cancers

Tumor ________________ stop cell division when something is not correct (ex. DNA damage)

Tumor suppressors stop cell division when something is not correct (ex. DNA damage)

leukemia

cancer of white blood cells.

sarcoma

cancers arising from connective tissue or muscle cells

carcinoma

cancers arising from epithelial cells (Most of our cells are these so 80% of cancers are these)

What percentage of the Human genome is conserved? What fraction of the amount is actually protein coding?

5%; 1/3

Gene repressor proteins are? They do not compete with?

Proteins that further regulate transcription do not compete with RNA polymerase

Proteins travel from the ________ in COPII-coated vesicles to the _________________

Proteins travel from the ER in COPII-coated vesicles to the Golgi

_______________ mediate membrane fusion _________ protein: ______________________________ or fusion protein first required to pry v-SNARE and t-SNARE apart

SNAREs mediate membrane fusion NSF protein: N-ethylmaleimide sensitive factor or fusion protein first required to pry v-SNARE and t-SNARE apart

___________________: large turbine-like protein machines; puts hydrogen into organelles

V-type pumps: large turbine-like protein machines; puts hydrogen into organelles

What is the purpose of translesion polymerases?

attaches to the DNA when damage is detected by the sliding clamp, and replaces the clamp, then it removes covalent modifications to excise and replace nucleotides **doesnt always put the right one.

•Chemoattraction/chemorepulsion:

attraction to an emitted chemical cue

Define aneuploidy.

different number of chromosomes. a loss or gain of chromosome, either sex chromosome (leads to sexual infantilism and mild retardation) or an autosome (leads to birth defects & mental retardation).

What is Mosaicism?

due to random X-inactivation, in which females have certain cells/organs that have different phenotypes (can be observed in female calico cats)

Cytoskeleton must be ____________ and ____________ to handle constant changes in the cells.

dynamic and adaptable

•Microtubules have "__________________" which is defined as sudden conversion from growth to shrinkage and vice versa as long as there is a uniform free subunit concentration

dynamic instability

imprinting:

silencing of a gene by methylation from either the paternal or maternal chromo. Either only the mother or father's genes are expressed

Cockayne's syndrome is a defect in what type of repair mechanism?

transcription coupled repair, NER

lymphoma

white blood cells and immature precursors proliferate; cancer of lymphocytes, in which the cancer cells are mainly found in lymphoid organs.

•__________-actin is in muscle, _______ and ____________ in all non-muscle cells

•Alpha-actin is in muscle, beta and gamma in all non-muscle cells

intermediate filaments are polar or not polar?

•Also, filaments are not polar (both ends of the proteins are the same)

encloses the DNA

Leucine zippers

What are the 4 protein structures?

primary, secondary, tertiary, quaternary

True/ false: All amyloid is bad.

False, not all amyloid is bad

Cyclin A

S Cyclin

What type of proteins does bad mRNA create?

aberrant protein

The primary cilium acts as a responder to ________________________

external environment

Kartagener syndrome: •paralyzed _______ so chronic lung disease due to insufficient movement of ________ from defect in __________ arms •embryonic developmental issues Mutations on two genes, __________ and _________ on chromosome ______, both of which code for proteins found in the ciliary outer _________ arm lead to this syndrome.

•paralyzed cilia so chronic lung disease due to insufficient movement of cilia from defect in dynein arms •embryonic developmental issues Mutations on two genes, DNAI1 and DNAH5 on chromosome 9, both of which code for proteins found in the ciliary outer dynein arm lead to this syndrome.

What is believed to be the reason(s) proteins move through the Golgi cisternae?

◦Unclear ◦Directional vesicular transport? Random transport? Cisternal maturation? Specialized SNAREs? theses are all possibilities

Think about Telophase: _____ sets of chromosomes are packaged into daughter nuclei •Disassembly of the ________________ •Re-formation of ______________ by coalescing around chromosome clusters and re-formation of __________; gets help from ______ •Contractile ________ formation •Lots of ______________ moves process backward (in a sense)

-2 sets of chromosomes are packaged into daughter nuclei •Disassembly of the mitotic spindle •Re-formation of nuclear envelope by coalescing around chromosome clusters and re-formation of pore complexes; help from ER •Contractile ring formation •Lots of dephosphorylation moves process backward (in a sense)

What happens during telophase?

-2 sets of chromosomes are packaged into daughter nuclei •Disassembly of the mitotic spindle •Re-formation of nuclear envelope by coalescing around chromosome clusters and re-formation of pore complexes; help from ER •Contractile ring formation •Lots of dephosphorylation moves process backward (in a sense)

-_______________ (microfilaments or "thin" filaments): a protein; cell surface shape, whole cell locomotion, links ________________ proteins to cytosolic proteins, pinches cell shut after division

-Actin (microfilaments or "thin" filaments): a protein; cell surface shape, whole cell locomotion, links transmembrane proteins to cytosolic proteins, pinches cell shut after division

-_________________: made of protein; positions organelles, intracellular transport, needed for cell division

-Microtubules: made of protein; positions organelles, intracellular transport, needed for cell division

Critical for control of muscle contraction: _______________ binds __________ which causes _________ (an accessory muscle protein) to move away from actin so it can bind to ___________ to shorten sarcomere and _____________ muscle.

-Calcium binds troponin which causes tropomyosin (an accessory muscle protein) to move away from actin so it can bind to myosin to shorten sarcomere and contract muscle

-G1 cyclins govern activities of __________________

-G1 cyclins govern activities of G1/S cyclins

-____________________ activate Cdks in late G1 to trigger progression through the _______________________ (commits to entry into cell cycle)

-G1/S-cyclins activate Cdks in late G1 to trigger progression through the restriction point (commits to entry into cell cycle)

What are the 4 classes of cyclins define by the stage of the cell cycle at which they bind CDks and function?

-G1/S-cyclins activate Cdks in late G1 to trigger progression through the restriction point (commits to entry into cell cycle) -S-cyclins bind Cdks to help stimulate chromosome replication and control early mitosis -M-cyclins activate Cdks that stimulate entry into mitosis -G1 cyclins govern activities of G1/S cyclins

-__________________: several proteins; provide mechanical strength, line inside of nuclear envelope

-Intermediate: several proteins; provide mechanical strength, line inside of nuclear envelope

____________ phosphorylates several subunits of nuclear pore complexes •initiation of ______________ disassembly •initiation of ________________ (intermediate filament lamin) dissociation •nuclear envelope broken into small ___________

-M-Cdk phosphorylates several subunits of nuclear pore complexes •initiation of pore complex disassembly •initiation of nuclear lamina (intermediate filament lamin) dissociation •nuclear envelope broken into small vesicles

-_____________________ activate Cdks that stimulate entry into mitosis

-M-cyclins activate Cdks that stimulate entry into mitosis

Think chromatid separation: -____________________ transition initiated by anaphase-promoting complex (__________) -_________ disrupted by APC/C via ___________ (protein) and activated ___________(enzyme), allowing chromatids to separate -_____- and _____-cyclins are destroyed and ______ are inactivated

-Metaphase-to-anaphase transition initiated by anaphase-promoting complex (APC/C) -Cohesins disrupted by APC/C via securin and activated separase, allowing chromatids to separate -S- and M-cyclins are destroyed and Cdks are inactivated

What are the accessory proteins involved with the cytoskeleton?

-Motor proteins (dynein, kinesin) with microtubules -Tubulins, mysosin, actinin, cadherin, vinculin, vimentin, desmin

-________________ bind Cdks to help stimulate chromosome ___________ and control early _____________

-S-cyclins bind Cdks to help stimulate chromosome replication and control early mitosis

What are the three major transitions in the cell cycle?

-Start (restriction point in late G1): cell commits to cell-cycle entry and chromosome duplication -G2/M: early mitotic events with chromosome alignment on the spindle occur; DNA repair too -Metaphase to anaphase transition: sister chromatids separate, anaphase triggered

________________ is measured clinically to determine whether an acute _______________________ (heart attack) has occurred

-Troponin is measured clinically to determine whether an acute myocardial infarction (heart attack) has occurred

•How does APC/C become activated?

-Unclear; process involves increased transcription of certain proteins (promoted by M-Cdk)

What are the 5 stages of M phase in Mitosis? What else happens to the cell in the M phase?

-prophase -prometaphase -metaphase -anaphase -telophase Cytokinesis

Which cell cycle transition(s) must cohesins be destroyed?

-these proteins must be destroyed during metaphase to anaphase transition

List off the ways that cells can control their own proteins...

-transcriptional control -RNA processing -RNA transport and localization -translation control -degradation control -protein activity control (phosphorylation)

Co-translational translocation ◦In __________, proteins are imported before they are completely ____________...ribosome is attached to ER via special particles and sequences

1. Co-translational translocation ◦In rER, proteins are imported before they are completely translated...ribosome is attached to ER via special particles and sequences

What are two common repair mechanisms? generally describe them

1. Base excision repair- DNA glycosylases are specific for altered DNA base. a. Hydrolysis occurs by specific glycosylase b. AP enzymes (apurinic or apyrimidic endonucleases) chew out sugar backbone here c. DNA polymerase adds new nucleotide d. DNA ligase seals nick with new sugar piece 2.Nucleotide Excision Repair- Recognition of dimer begins this repair. a. Helicase unwinds local duplex b. excision nuclease cleaves both sides of the damage leaving a gap of ~30 nucleotides c. DNA polymerase and ligase finish the job.

What are the two processes in translation?

1. Co-translational translocation 2. Post-translational translocation (not an ER process)

State 3 differences between RNA and DNA

1. DNA is double stranded 2. RNA has Uracil and DNA has Thymine 3. RNA have a ribose sugar and DNA has deoxyribose sugar.

Causes: > Stressed out cells die when there is: (there are 7)

1. Glucocorticoid binding of nuclear receptors 2. Radiation 3. Heat 4. Nutrient deprivation 5. Viral infection 6. Hypoxia 7. High intracellular calcium

What are the three classes of ATP Driven pumps?

1. P-type pumps 2. ABC transporters 3. V-type pumps

What are the 6 ways of gene regulation? list in order. **hint remember the image.

1. Transcriptional control 2. RNA processing control 3. RNA transport and localization control 4. translation control 5. mRNA degradation control 6. protein activity control

What are the two main classes of membrane proteins that mediate molecular traffic?

1. Transporters that have moving parts (some are called carriers, some are "pumps") 2. Channels that form pores; weaker interaction

Multiple breakdowns of signaling: 1.Cell division occurs in response to _____________ signals 2.DNA is repaired via _____________ 3.Cells make connections with ________________ 4.If connections change, neighboring cells create a _________ boundary 5.If cell is beyond repair, _____________

1.Cell division occurs in response to external signals 2.DNA is repaired via enzymes 3.Cells make connections with neighbors 4.If connections change, neighboring cells create a tissue boundary 5.If cell is beyond repair, apoptosis

What are the 2 steps of initiation of replication?

1.During late mitosis and early G1, prereplication complex (pre-RC) assembles by ORCs (called "licensing") 2.At onset of S phase, pre-RCs induce formation of preinitiation complex which unwinds the DNA helix and loads DNA polymerases

What are the 9 functions of proteins?

1.Tissue nutrition 2.Water distribution (balance) 3.Plasma buffer 4.Substance transport 5.Structural support 6.Antibodies, coagulation, hormones 7.Enzymes 8.Movement 9.Membrane receptors and transport

BH123 protein

made up of subunits Bak and Bax, and is a pro-apoptotic protein

In the 1st step of initiation of replication: During late mitosis and early G1, ______________________ assembles by ORCs (called "_______________") •_____________ inhibits this step, so it happens when this Cdk complex (___________ and _______) is low •APC/C stimulates this step, so it happens when APC/C is _______ (high or low); G1/S complex with high cyclin ________.

1During late mitosis and early G1, prereplication complex (pre-RC) assembles by ORCs (called "licensing") •M-Cdk inhibits this step, so it happens when this Cdk complex (cyclin M and CdK 1) is low •APC/C stimulates this step, so it happens when APC/C is high; G1/S complex with high cyclin G1

Xeroderma pigmentosum

A defect in one of several DNA repair genes is expressed as a dysfunctional repair enzyme...this is heritable as the mutation occurs in the germ line. Skin cell mutations persist, resulting in tumors.

A ___________________ is a round matrix of protein with a pair of centrioles. Around the surface are nucleating sites of _______________ complexes. This is where ________________ grow from, like pins in a pin cushion.

A centrosome is a round matrix of protein with a pair of centrioles. Around the surface are nucleating sites of gamma tubulin ring complexes. This is where microtubules grow from, like pins in a pin cushion.

What is a pyrimidine dimer and what do they involve?

A cyclobutane ring that causes distortions in the DNA helix by pulling together two thymine bases close together

A growing microtubule has ______-containing subunits at its end, forming a ___________. If nucleotide ____________ proceeds more rapidly than subunit additions, the cap is lost and _____________ begins to shrink (called a _____________). ________-containing subunits may still add to the shrinking end, and if a new cap forms, then microtubule growth resumes (called __________).

A growing microtubule has GTP-containing subunits at its end, forming a GTPcap. If nucleotide hydrolysis proceeds more rapidly than subunit additions, the cap is lost and microtubule begins to shrink (called a catastrophe). GTP-containing subunits may still add to the shrinking end, and if a new cap forms, then microtubule growth resumes (called rescue).

__________________: largest family of membrane proteins

ABC transporters: largest family of membrane proteins

Actin subunits are ___________ and have structurally different ends -Slower-growing ________ end (__________ end) -Faster-growing ________ end (_________ end)

Actin subunits are polar and have structurally different ends -Slower-growing minus end (pointed end) -Faster-growing plus end (barbed end)

Actin subunits have a shape that resembles an _______________. this complex is formed between ________________ and the motor protein __________.

Actin subunits have a shape that resembles an arrowhead. this complex is formed between actin filaments and the motor protein myosin.

•APC/C is the _______________ or anaphase promoting complex -It is a _______________ ____________ that catalyzes the destruction of major proteins: ____________ (protects protein links between sister chromatids and unleashes anaphase) and S- and M-cyclins

APC/C is the cyclosome or anaphase promoting complex -It is a ubiquitin ligase that catalyzes the destruction of major proteins: securin (protects protein links between sister chromatids and unleashes anaphase) and S- and M-cyclins

ATP- Driven Pumps called transport _______________ as they involve ____________ of ATP to ADP and _____________ with use of resultant energy to pump ions or other things across a membrane

ATP- Driven Pumps called transport ATPases as they involve hydrolysis of ATP to ADP and phosphate with use of resultant energy to pump ions or other things across a membrane

___________________________ is a congenital disorder that results in defects in the structure of the Golgi apparatus > Mutation in the _____________ gene > Affects _____________ and __________ development > Affected infants have extremely short limbs, a narrow __________, short ribs that fracture easily, and a lack of normal bone formation (________________) in the _______, spine, and _____________

Achondrogenesis is a congenital disorder that results in defects in the structure of the Golgi apparatus > Mutation in the TRIP11 gene > Affects cartilage and skeletal development > Affected infants have extremely short limbs, a narrow chest, short ribs that fracture easily, and a lack of normal bone formation (ossification) in the skull, spine, and pelvis

Actin web formation. A new branch is built from the ____________ proteins, which form a 70 degree angle. New actin filaments are added on the ________ end, with the ________ end attached to the_______.

Actin web formation. A new branch is built from the Arp 2/3 proteins, which form a 70 degree angle. New actin filaments are added on the plus end, with the minus end attached to the Arp.

What are the 3 types of cytoskeletal proteins?

Actin, Mictrotubules, and intermediate filaments

_____________ are proteins that bind cis-regulatory sequences (formerly "enhancer" sequences) that can be far away from the gene.

Activator Proteins

transcriptional synergy

Activator proteins work together with other proteins synergistically to increase the rate of transcription.

_______________ is an uphill process, requiring transporters to be linked to energy

Active transport is an uphill process, requiring transporters to be linked to energy

What two structures are considered secondary structures?

Alpha helix and beta sheet

Alteration and accumulation of these intermediate filaments (_____________) in neurons lead to ________ (disease).

Alteration and accumulation of these intermediate filaments (neurofilaments) in neurons lead to ALS (disease).

oncogene

An altered gene whose product can act in a dominant fashion to help make a cell cancerous. Typically, an oncogene is a mutant form of a normal gene (proto-oncogene) involved in the control of cell growth or division.

An ______________ signal activates _______, which triggers NOXA, PUMA, BAK, and BAX. Anti-apoptotic proteins are negative regulators such as _________, _________, and ________. If apoptosis proceeds, this affects the _________________, in which _______________ and _________ form an aptosome with caspase ___. Along with the other caspases, apoptosis occurs.

An apopotic signal activates p53, which triggers NOXA, PUMA, BAK, and BAX. Anti-apoptotic proteins are negative regulators such as BCL-2, BCL-X, and MCL1. If apoptosis proceeds, this affects the mitochondria, in which cytochrome C and ApaL-1 form an aptosome with caspase 3. Along with the other caspases, apoptosis occurs.

An _____________ signal causes ______________ of adapter proteins. The initiator caspase _____ and _____ is cleaved. The active caspase structure is called the _______________ caspase, which cleaves multiple substrates leading to ______________.

An apoptotic signal causes dimerization of adapter proteins. The initiator caspase 8 and 9 is cleaved. The active caspase structure is called the executioner caspase, which cleaves multiple substrates leading to apoptosis.

Anaphase segregation of chromosome: two ___________(dependent or independent) overlapping processes -anaphase _____ is separation of _________ poles -anaphase _____ is initial pole ward movement of __________________

Anaphase segregation of chromosome: two independent yet overlapping processes -anaphase B is separation of spindle poles -anaphase A is initial pole ward movement of chromosomes

What chromosome disorder has the following: Isochrome formation: caused by the isochromosome 15, paternal Clinical features: passed down by parents.

Angelman

Bcl2 protein

Anti-apoptotic protein that is required for intrinsic pathway

__________________ proteins can block cell death such as ________

Anti-apoptotic proteins can block cell death such as BCL-2

Apoptosis and Disease: > ____________: tumorigenic cells regulate the apoptotic pathway abnormally §Bcl2 production increases after a chromosomal ___________________, leading to _____________ inhibition of those cells (__________________) §________ gene mutated in many cancers so no cell death or cell-cycle arrest = ___________ §Cells lose _____________ to neighbor cells

Apoptosis and Disease: >Cancer: tumorigenic cells regulate the apoptotic pathway abnormally §Bcl2 production increases after a chromosomal translocation, leading to apoptotic inhibition of those cells (lymphocytes) §P53 gene mutated in many cancers so no cell death or cell-cycle arrest = tumors §Cells lose adherence to neighbor cells

Apoptosis follows a very different pathway as compared to ______________ (cell death in response to acute issue)

Apoptosis follows a very different pathway as compared to necrosis (cell death in response to acute issue)

_______________ is programmed cell death

Apoptosis is programmed cell death

Apoptotic Cells are Recognizable: >Morphologically >>___________ membrane due to cell shrinkage >>Nucleus ____________ and ________________ >>______________ dissolves >>Cell breaks apart with intact _____________ to form ________________ bodies

Apoptotic Cells are Recognizable: Morphologically >Blebbed membrane due to cell shrinkage >Nucleus condenses and fragments >Cytoskeleton dissolves >Cell breaks apart with intact membranes to form apoptotic bodies

At any point, cell cycle progression can be arrested if _________ is irreparably ___________ OR if environments are not _____________.

At any point, cell cycle progression can be arrested if DNA is irreparably damaged OR if environments are not favorable

In the 2nd step of initiation of replication: At onset of S phase, pre-RCs induce formation of ____________________ which unwinds the DNA helix and loads ____________________. •____________ is activated and triggers preinitiation complex •Elevated ____________ keeps Step #1 from happening until early G1

At onset of S phase, pre-RCs induce formation of preinitiation complex which unwinds the DNA helix and loads DNA polymerases •S-CdK is activated and triggers preinitiation complex •Elevated S-Cdk keeps #1 from happening until early G1

_________________: core of cilium/flagellum

Axoneme

Which of the following parts of the cell cycle is known as the Restriction Point (also known as Start)? a. G2/ M transition b. metaphase to anaphase transition c. Late G1 d. G1/G2 transition

C. late G1

What chromosome disorder has the following: Chromosomal translocation in chromosomes 9 and 22. Clinical features: is a bone marrow disease characterized by increased proliferation of a WBC line, and is responsible for 20% of adult leukemia.

CML (Chronic Myelogenous Leukemia)

COPII-coated vesicles >> Membrane-bound, active ____________ recruits COPII adapter proteins and cause the membrane to ______________. >> The __________ proteins then recruit the outer coat proteins which help form a _________. >> A subsequent membrane ___________ event pinches off the coated ____________.

COPII-coated vesicles >> Membrane-bound, active Sar1-GTP recruits COPII adapter proteins and cause the membrane to deform. >> The adaptor proteins then recruit the outer coat proteins which help form a bud. >> A subsequent membrane fusion event pinches off the coated vesicle.

Cancer Cell Immortality ¢Tumor cells overcome replicative cell ________________________ (cell __________ after a specific number of cell divisions) by activating ______________ which replaces the _________________ segments that are lost during each cell division >> Changes in cancer cells disable _____________________ controls so cell cycle never _____________. >> _______________________ activity is maintained

Cancer Cell Immortality ¢Tumor cells overcome replicative cell senescence (cell death after a specific number of cell divisions) by activating telomerase which replaces the telomere segments that are lost during each cell division >> Changes in cancer cells disable checkpoint controls so cell cycle never stops >> Telomerase activity is maintained

Cancer Cells ¢Are genetically _______________: continue to accumulate more ________________ or deletions or develop crazy chromosome issues more than normal cells ¢Have abnormal ______________ control ¢Lose their ___________________ (look like stems) ¢Have defective ___________ control ¢Utilize _____________ at a much higher level ¢Continue dividing despite _________ damage ¢Avoid replicative _________________ through p53 mutation or _________________ maintenance ¢Must survive in a ______________ environment

Cancer Cells ¢Are genetically unstable: continue to accumulate more point mutations or deletions or develop crazy chromosome issues more than normal cells ¢Have abnormal growth control ¢Lose their differentiation (look like stems) ¢Have defective death control ¢Utilize glucose at a much higher level ¢Continue dividing despite DNA damage ¢Avoid replicative senescence through p53 mutation or telomerase maintenance ¢Must survive in a foreign environment

Cancer is uncontrolled cell _________________ that spreads to other tissues due to multiple genetic ____________.

Cancer is uncontrolled cell division that spreads to other tissues due to multiple genetic defects

Cancer therapies take many forms, with varying levels of ________________

Cancer therapies take many forms, with varying levels of targeting

Cancer vaccines Immune "_______________" inhibitor protein drugs release ____________ from holding back on killing ______________ cells; used to treat many cancers (ckpoint proteins include PD-____, PD-_____, CTLA-_____) >> _______________®: any microsatellite instability-high or strand mismatch repair deficient solid tumor >> _______________®: same as above but mostly colorectal cancers _________________ vaccines: stop or delay cancer cell growth, cause tumor shrinkage, or eliminate cells >> _________________®: stimulates immune system using patient's own cancer cells or their antigen-presenting cells mixed with proteins

Cancer vaccines Immune "checkpoint" inhibitor protein drugs release T-cells from holding back on killing cancer cells; used to treat many cancers(ckpoint proteins include PD-1, PD-L1, CTLA-4) >> Keytruda®: any microsatellite instability-high or strand mismatch repair deficient solid tumor >> Opdivo®: same as above but mostly colorectal cancers Therapeutic vaccines: stop or delay cancer cell growth, cause tumor shrinkage, or eliminate cells >> Provenge®: stimulates immune system using patient's own cancer cells or their antigen-presenting cells mixed with proteins

___________, with cell growth and division despite absence of signal and loss of self-destruction; other new signals allow _______________.

Cancers, with cell growth and division despite absence of signal and loss of self-destruction; other new signals allow angiogenesis

___________________: a collection of disorders that share two properties: cell reproduction and division despite various restraints and controls AND invasion _________________: mass of cells or tumor; if benign, then there is no invasion _________________ neoplasms invade nearby tissues Malignant ________________ are made up of cells from a single ancestor; they are _________________ in origin and form the "_____________________" If malignant and invasive, the cells ______________ (spread) to more distant sites in the body to form secondary tumors; THIS IS _________________.

Cancers: a collection of disorders that share two properties: cell reproduction and division despite various restraints and controls AND invasion Neoplasm: mass of cells or tumor; if benign, then there is no invasion Malignant neoplasms invade nearby tissues Malignant neoplasms are made up of cells from a single ancestor; they are monoclonal in origin and form the "primary tumor" If malignant and invasive, the cells metastasize (spread) to more distant sites in the body to form secondary tumors; THIS IS CANCER

What antigen is found in certain colon cancers? What antigen is found in liver cancer?

Carcinoembryonic antigen (CEA) Alpha- fetoprotein

Caspase Activation: > A "_____________" must be received §____________ domains with ________________ domain allows them to assemble with "____________" proteins into activation complexes ▪Proximity of _______________ procaspases activates them (they ___________ each other); this begins the cascade ▪________________ procaspases are activated and ____________ is amplified > __________ signal pathways: Which are?

Caspase Activation: ¡A "death signal" must be received §Procaspase domains with recruitment domain allows them to assemble with "adaptor" proteins into activation complexes ▪Proximity of initiator procaspases activates them (they cleave each other); this begins the cascade ▪Executioner procaspases are activated and death signal is amplified ¡Two signal pathways: Extrinsic/ intrinsic pathway

Caspases are located in _____________ as inactive ____________

Caspases are located in cytoplasm as inactive procaspases

______________ are proteases with a ____________ at their active site and that cleave target substrates at a specific ____________________.

Caspases are proteases with a cysteine at their active site and that cleave target substrates at a specific aspartic acid

Caspases play a role in both _____________ and ___________ pathways

Caspases play a role in both extrinsic and intrinsic pathways

_______________ (speed up reactions) that permit cells to make and break covalent bonds

Catalysts

Cell movement Interactions: __________ and __________ are bound together. _____________ bind to extracellular matrix. ___________ is polymerized on ________ end (end of protrusion). ___________ proteins can bind the integrins to the actin, allowing traction for forward movement.

Cell movement Interactions: Actin and myosin are bound together. Integrins bind to extracellular matrix. Actin is polymerized on plus end (end of protrusion). Adapter proteins can bind the integrins to the actin, allowing traction for forward movement.

Cell response to extracellular signal: ______________ response: if changes occur to proteins already present within cell; altered protein ________________ ____________ response: if changes to gene expression or new protein synthesis are required; altered protein _______________

Cell response to extracellular signal: Fast response: if changes occur to proteins already present within cell; altered protein function Slow response: if changes to gene expression or new protein synthesis are required; altered protein synthesis

Cells membranes allow _________ and _________________ molecules to diffuse across

Cells membranes allow water and nonpolar molecules to diffuse across

_________________ is a microtubule organizing center with embedded ______________ and nucleation sites: important during ____________

Centrosome is a microtubule organizing center with embedded centrioles and nucleation sites: important during mitosis

Charcot-Marie-Tooth Disease _______________ disorder appears in legs first, then moves to arms with eventual sensory symptoms often appearing in mid-childhood ◦___________________ and motor nerves lose ability to transmit nervous impulses ◦1 in ____________ affected, common disorder ◦Possible 40 different genes involved, leading to damage in _______________ around _____________ nerves; different inheritance patterns >> Most common cause is duplication of a region on chromosome _______ that contains a gene for making myelin in peripheral nerve cells, causing _____________ destabilization

Charcot-Marie-Tooth Disease Motor nerve disorder appears in legs first, then moves to arms with eventual sensory symptoms often appearing in mid-childhood ◦Peripheral sensory and motor nerves lose ability to transmit nervous impulses ◦1 in 2500 affected, common disorder ◦Possible 40 different genes involved, leading to damage in myelin sheath around peripheral nerves; different inheritance patterns >> Most common cause is duplication of a region on chromosome 17p that contains a gene for making myelin in peripheral nerve cells, causing myelin destabilization

Chemical Changes: ¡Chemically >DNA is fragmented by an __________________ at the linker regions between ______________ >Membrane phospholipid __________________ changes conformation and moves to outer leaflet of ________________ >Release of mitochondrial ________________ into cell cytosol >Vacuole formation related to organelle _________________

Chemical Changes: ¡Chemically >DNA is fragmented by an endonuclease at the linker regions between nucleosomes >Membrane phospholipid phosphatidylserine changes conformation and moves to outer leaflet of lipid bilayer >Release of mitochondrial cytochrome c into cell cytosol >Vacuole formation related to organelle autophagy

Define and explain chromatin/chromosome territories within a cell nucleus:

Chromatins move around in the nucleus, and chromosomes are located within the nucleus as well, but these locations can change depending on the level of expression required of the gene on that chromosome! Gene-rich regions of the chromosome tend to move centrally into the nucleus where the appropriate region exists. (during active transcription, a gene loops out into the center of the nucleus where transcription proteins are located)

Classification of cancer: ____________________: cancers arising from ________________ cells (Most of our cells are these so 80% of cancers are these) >>___________________ is a benign tumor arising from epithelial cells in a gland _____________________: cancers arising from connective tissue or muscle cells _____________ or ________________: white blood cells and immature precursors proliferate

Classification of cancer: Carcinoma: cancers arising from epithelial cells (Most of our cells are these so 80% of cancers are these) >>Adenoma is a benign tumor arising from epithelial cells in a gland Sarcoma: cancers arising from connective tissue or muscle cells Lymphoma or leukemia: white blood cells and immature precursors proliferate

MSH2, 3, 6, MLH1, PMS2: What is the phenotype and enzyme or process affected?

Colon cancer Mismatch repair

Communication between cells is mediated by ____________ signal molecules

Communication between cells is mediated by extracellular signal molecules

_________________ refers to the number of sequences, proteins, and stretches of DNA looped and spaced out, which is needed to control a gene.

Complex switches:

What is the protein that avoids sister chromatid breakage and compacts the chromatids?

Condensin

Condensin is a protein used to avoid sister chromatid breakage, ________________ (compaction of chromatids) and _______________ (resolved into separable units) must occur

Condensin is a protein used to avoid sister chromatid breakage, condensation (compaction of chromatids) and resolution (resolved into separable units) must occur

______________________: signal remains attached to cell surface receptor of the signaling cell and influences only those cells it contacts This is important during ______________ and _______________________.

Contact Dependent Signaling: signal remains attached to cell surface receptor of the signaling cell and influences only those cells it contacts Important during development and immune response

Copying (or ___________________) of a single strand of DNA to form a second strand of DNA is called "________________." The ______________ bonds between the bases are relatively weak and can be pulled apart (by an enzyme) without messing with the sugar-phosphate backbone.

Copying (or templated polymerization) of a single strand of DNA to form a second strand of DNA is called "replication." The hydrogen bonds between the bases are relatively weak and can be pulled apart (by an enzyme) without messing with the sugar-phosphate backbone.

What are the three types of active transport?

Coupled transport ATP driven pumps Light- or redox-driven pumps

What chromosome disorder has the following: Deletion: p arm of chromosome 5 Clinical features: profound retardation(IQ <20), voice of a crying cat, and physical issues.

Cri-du-Chat

•Cyclin-dependent ______________ are protein enzymes that add _______________ to various proteins involved in cell cycling

Cyclin-dependent kinases are protein enzymes that add phosphates to various proteins involved in cell cycling

____________ are proteins that activate the Cdks to do their thing; They are activated by specific cues such as _______________ or __________________ signals such as growth factors, hormones, etc.

Cyclins are proteins that activate the Cdks to do their thing; cyclins are activated by specific cues such as cell size or intra/extracellular signals such as growth factors, hormones, etc.

Cytoskeletal structures help maintain membrane structure and function by ____________ certain proteins in regions or _________.

Cytoskeletal structures help maintain membrane structure and function by corralling certain proteins in regions or rafts

Disorders of the ER include___________________ Disease and _______________________.

Disorders of the ER include Charcot-Marie-Tooth Disease and Multiple Sclerosis

DNA is synthesized on a __________________ that is a pre-existing DNA strand, with __________________ bonds formed between the bases (which exhibit very specific pairing)

DNA is synthesized on a template that is a pre-existing DNA strand, with hydrogen bonds formed between the bases (which exhibit very specific pairing)

__________________ makes short RNA pieces or primers (10 nucleotides long) on the lagging strand

DNA primase

___________________________ are those that assure accurate replication of DNA; ______ is good example of this If mutated, these genes that encode specific proteins cause genomic instability (widespread ________________, _________________ breaks, ________________). When these mutations affect pathways that regulate cellular________________, a __________ may arise

DNA repair genes are those that assure accurate replication of DNA; p53 is good example of this If mutated, these genes that encode specific proteins cause genomic instability (widespread mutations, chromosome breaks, aneuploidy). When these mutations affect pathways that regulate cellular proliferation, a tumor may arise

cis-regulatory sequence:

DNA sequence that has a transcription regulator protein bound to it, usually located shortly upstream of gene and always on same chromo; these specify time and place gene is to be transcribed (activator or repressor proteins); genes have many regulator sequences).

Promoters such as the TATA box are...

DNA sequences immediately upstream of a gene that are binding sites for transcription factors. (Concerted stepwise assembly of many transcription factors at the promoter site can change rate of transcription initiation) The mediator connects all

Genes are made up of _______ and about ____% make up the human genome.

DNA, 1.2%

_______ can be described as an "information archive" and _________ is an "expendable information carrier".

DNA, RNA

_____________ pathways can be extrinsic or intrinsic

Death pathways can be extrinsic or intrinsic

___________ ___________ genes are repressed after normal embryonic development. What protein does this? When these embryonic proteins are re-expressed it can forma tumor called?

Developmental regulatory genes gene repressor proteins oncofetal antigens

Disorders of Golgi Apparatus > Group of ____________________________ disorders caused by mutation in genes encoding glycosylating enzymes or transport proteins ◦Lethal by age ______ ◦Called "________________________" in which proteins are excreted instead of going to ____________________; a type of _______________________ disease since no __________________ in lysosomes > In _____________________ disease, neuronal Golgi fragments and atrophies

Disorders of Golgi Apparatus > Group of congenital glycosylation disorders caused by mutation in genes encoding glycosylating enzymes or transport proteins ◦Lethal by age 2 ◦Called "inclusion-cell disease" in which proteins are excreted instead of going to lysosomes; a type of lysosomal storage disease since no hydrolases in lysosomes > In Alzheimer disease, neuronal Golgi fragments and atrophies

Disorders of Nonsense Mutations Rare; caused by _______________ protein because STOP codon is misplaced. List a few diseases: > Certain cystic fibrosis mutations > Duchenne's MD > Beta-thalassemia > Hurler's syndrome

Disorders of Nonsense Mutations Rare; caused by truncated protein because STOP codon is misplaced > Certain cystic fibrosis mutations > Duchenne's MD > Beta-thalassemia > Hurler's syndrome

What chromosome disorder has the following: Aneuploidy: Extra chromosome 21, trisomy Isochrome: isochromosome arm in 21q type [46, XY,i(21)(q10)] Clinical features: Hypotonia, mental retardation, short stature, prematurity, flat nasal bridge, simian crease.

Down Syndrome

Drug Targets ¢How are targets identified? >> Growth or survival proteins present in greater abundance in ___________ cells (____________) >> _________________ proteins that drive cancer progression (__________ is a cell growth protein, but BRAFV600E is ___________) >> ____________________ abnormalities in cancer cells (fusion protein production such as __________________)

Drug Targets ¢How are targets identified? >> Growth or survival proteins present in greater abundance in cancer cells (HER-2) >> Altered proteins that drive cancer progression (BRAF is a cell growth protein, but BRAFV600E is altered) >> Chromosomal abnormalities in cancer cells (fusion protein production such as BCR-ABL)

Dysregulation of ________________ and endothelial cell interaction contributes to cancer, vascular occlusion in sickle cell, sepsis, etc.

Dysregulation of leukocyte adhesion and endothelial cell interaction contributes to cancer, vascular occlusion in sickle cell, sepsis, etc.

ER Problems If too many un- or misfolded proteins _________________ in or near ER, ER becomes "_______________", possibly beginning an _________________ response in cells to eliminate those cells ◦____________ or ___________ inhibits translation of many proteins, but upregulates chaperones; _________ (master regulator) issue ◦Occurs mostly in _______________ system where myelinating cells produce much __________________ in the myelinating process ◦Involved in _______________ of myelin disorders like __________________ disease and MS

ER Problems If too many un- or misfolded proteins accumulate in or near ER, ER becomes "stressed", possibly beginning an apoptotic response in cells to eliminate those cells ◦ERSR or UPR inhibits translation of many proteins, but upregulates chaperones; BiP (master regulator) issue ◦Occurs mostly in nervous system where myelinating cells produce much plasma membrane in the myelinating process ◦Involved in pathogenesis of myelin disorders like Charcot-Marie-Tooth disease and MS

ER Transport >> Exit signals on ________________ tails of ____________ proteins interact with soluble ER proteins and membrane cargo ________________. >> These complex into the budding transport vesicle, interacting with _____________ and _____________ proteins

ER Transport >> Exit signals on cytosolic tails of cargo proteins interact with soluble ER proteins and membrane cargo receptors >> These complex into the budding transport vesicle, interacting with Sar1-GTP and COPII proteins

ER proteins that have escaped are returned in vesicles using ______________________ signals and receptors

ER proteins that have escaped are returned in vesicles using retrograde transport signals and receptors

Which type of signaling is described? A cell releases a soluble molecule into the bloodstream to have an effect on a different organ system. a. Paracrine b. Endocrine c. Contact-dependent d. Synaptic

Endocrine

______________: Hormonal system cells synthesize and release chemical (protein, steroid, amine-derived) hormones into bloodstream to affect distant targets

Endocrine: Hormonal system cells synthesize and release chemical (protein, steroid, amine-derived) hormones into bloodstream to affect distant targets

_______________________: interconnected network of tubules, vesicles, and cisternae known as the "_____________________" of the eukaryotic Cells.

Endoplasmic Reticulum: interconnected network of tubules, vesicles, and cisternae known as the "transportation system" of the eukaryotic Cells.

______________________ is a disease due to genetic defect in keratins; skin ruptures or blisters with any mechanical stress.

Epidermolysis Bullosa is a disease due to genetic defect in keratins; skin ruptures or blisters with any mechanical stress.

Escaped proteins > Why would some proteins have to be returned to the ER? > The ER is _____________ and some proteins escape inappropriately > Resident ER proteins have retrieval signals that bind ____________ coats and are packaged into vesicles for ________________ delivery to ER > _____________________ include lysine-lysine-any aa-any aa (____________) and Lys-Asp-Glu-Leu (__________) > ______________ receptors in the tubular clusters and Golgi capture the escaped _______________ and carry them back to ER in ____________ coated vesicles

Escaped proteins > Why would some proteins have to be returned to the ER? > The ER is leaky and some proteins escape inappropriately > Resident ER proteins have retrieval signals that bind COPI coats and are packaged into vesicles for retrograde delivery to ER > Retrieval signals include lysine-lysine-any aa-any aa (KKXX) and Lys-Asp-Glu-Leu (KDEL) > KDEL receptors in the tubular clusters and Golgi capture the escaped protein and carry them back to ER in COPI-coated vesicles

___________________ activity for excision of mismatched bases is provided by DNA polymerase

Exonucleolytic

______________________: These are either membrane bound molecules (need direct contact with target)or are released into extracellular space by ______________ or diffusion into extracellular space

Extracellular Signals: These are either membrane bound molecules (need direct contact with target)or are released into extracellular space by exocytosis or diffusion into extracellular space

____________________________ molecules bind cell surface receptors to cause a cascade of signals inside the cell

Extracellular signaling molecules bind cell surface receptors to cause a cascade of signals inside the cell

Extracellular signals bind specific receptors on cell surface (_______________ proteins) or other places in a cell

Extracellular signals bind specific receptors on cell surface (transmembrane proteins) or other places in a cell

Extrinsic Pathway of Apoptosis: §_______________ signal proteins bind to death receptors on a cell ___________ ▪Receptors have ___________-binding region, one ________________ domain and a __________ domain ▪Receptors belong to ______ receptor family §Binding ligands belong to the ____________________ family ▪______________ initiates cascade of events within cell

Extrinsic Pathway of Apoptosis: §Extracellular signal proteins bind to death receptors on a cell surface ▪Receptors have ligand-binding region, one transmembrane domain and a death domain ▪Receptors belong to TNF receptor family §Binding ligands belong to the TNF signal protein family ▪Binding initiates cascade of events within cell

Which eukaryotic polymerases are replicative? .. for repairs? ...for Translesion polymerases?

Family B: alpha, sigma, and epsolon are replicative Family X: beta, mew, and lambda are repairs Family Y: n,l,k, and zeta are translesion poly, they arent too great because they dont have any exonucleolytic activity and dont discriminate about which nucleotide to add. ** these come in to rescue Family B during replication

___________ bind G proteins, which bind ______ and activate effector proteins such as _____________.

GPCRs bind G proteins, which bind GTP and activate effector proteins such as cyclic AMP

From ER to Golgi How do the proteins get from the ER to the Golgi? ◦If they are properly folded and assembled, they are packaged into ______________________ (coat-protein complex) coated transport __________________ that bud from ER membrane, then head to the Golgi How do proteins get into the transporters? ◦Selective process: some proteins have a exit (____________) signals that the COP II coat sees ◦Loss of ________________can lead to various disorders (fat absorption, protein secretion) ◦Some proteins are ______________ and only need a receptor on the ER membrane ◦Proteins without _______________ can leak out of the ER

From ER to Golgi How do the proteins get from the ER to the Golgi? ◦If they are properly folded and assembled, they are packaged into COP II (coat-protein complex) coated transport vesicles that bud from ER membrane, then head to the Golgi How do proteins get into the transporters? ◦Selective process: some proteins have a exit (transport) signals that the COP II coat sees ◦Loss of transporters can lead to various disorders (fat absorption, protein secretion) ◦Some proteins are soluble and only need a receptor on the ER membrane ◦Proteins without exit signals can leak out of the ER

What is the structure and function of nucleosomes?

Function & structure: the function of nucleosomes is to tightly wrap the DNA around the histone cores to help take up less space inside of the nucleus. They are also the basic unit of chromatins! The structure is about 200bp of DNA wrapped around, and it contains 2 each of 4 histone subunits called a histone octamer.

Function of the Golgi complex in eukaryotic cells: ◦Synthesis of __________________, sorting and exporting ER products, synthesis of ______________________________ (GAGs) ◦Primarily modifies proteins delivered from the rough ER through __________________ (does ______-linked _________________) and phosphorylation; particularly important in the processing of _______________ for secretion ◦Involved in the creation of _______________, ________________ (immature version of the answer prior)

Function of the Golgi complex in eukaryotic cells: ◦Synthesis of carbohydrates, sorting and exporting ER products, synthesis of glycosoaminoglycans (GAGs) ◦Primarily modifies proteins delivered from the rough ER through glycosylation (does O-linked glycosylation)and phosphorylation; particularly important in the processing of proteins for secretion ◦Involved in the creation of lysosomes, endosomes

G-protein structure is composed of 3 subunits: _____, _______ and _____; α (a _________) binds GDP and keeps G protein ________ but then releases GDP and binds _______ which activates G protein

G-protein structure is composed of 3 subunits: α, β and γ; α (a GTPase) binds GDP and keeps G protein inactive but then releases GDP and binds GTP which activates G protein

G-proteins are considered to be __________________ or _____________ based in part on the activation of ________________ (increases cAMP) or inhibition (decreases cAMP) of it Adenylyl cyclase synthesizes _________ which is how some extracellular signals work to mediate a cellular response

G-proteins are considered to be stimulatory or inhibitory based in part on the activation of adenylyl cyclase (increases cAMP) or inhibition (decreases cAMP) of it Adenylyl cyclase synthesizes cAMP which is how some extracellular signals work to mediate a cellular response

G-proteins are ____________ GTP-binding proteins attached to ________________ face of cell membrane

G-proteins are trimeric GTP-binding proteins attached to cytoplasmic face of cell membrane

Cyclin D

G1 Cyclin

In what phase is DNA replication "initiated"?

G1 phase

The eukaryotic cell cycle consists of 4 distinct phase, what are they?

G1 phase, S phase (synthesis), G2 phase (collectively known as interphase), and M phase (mitosis and cytokinesis)

Cyclin E

G1/S Cyclin

For Tay- Sachs, what other name does it go by, what mutations, clinical symptoms, and what accumulates and where?

Gangliosidosis, genetic mutation leads to a deficiency of hexosaminidase resulting in severe mental retardation with hearing and vision loss accumulation of gangliosides in brain.

Name the 4 lysosomal storage diseases talked about in lecture:

Gaucher disease Tay- Sachs (gangliosidosis) Metachromatic leukodystrophy (MLD) Hurler syndromes

______________ proteins tend to be rounded and bulky while ___________ proteins are filamentous (considered to be _______________ filaments) Gives some examples of the two mentioned above:

Globular, fibrous intermediate - globular: hemoglobin, enzymes, plasma proteins -fibrous: fibrinogen, collagen, troponin

_______________________: synthesis of carbohydrates and glycosaminoglycans (GAGs), sorting and exporting ER products

Golgi apparatus: synthesis of carbohydrates and glycosaminoglycans (GAGs), sorting and exporting ER products

Golgi processing occurs in order, moving from __________ to _______________

Golgi processing occurs in order, moving from cis to trans

2 alpha helices with a recognition sequence (has a kink in it which allows it to fit in to the groves of the DNA)

Helix turn Helix

Golgi structure: ◦Composed of membrane-bound stacks known as ________________ ◦Between _____ and ______ are usually present ◦Cisternae stack has five functional regions: the ___________________, _____________, _______________, _______________, and _______________________; each has specific enzymes on membrane surface ◦________________ move sequentially through the five regions

Golgi structure: ◦Composed of membrane-bound stacks known as cisternae ◦Between five and eight are usually present ◦Cisternae stack has five functional regions: the cis-Golgi network, cis-Golgi, medial-Golgi, trans-Golgi, and trans-Golgi network; each has specific enzymes on membrane surface ◦Proteins move sequentially through the five regions

_____________ cones: find and form connections with other cells •Tips of these are called ______________ filled with actin; ____________ is required for contraction of cell •These cones grow because of _________ factors and other substances on/in a _______________

Growth cones: find and form connections with other cells •Tips of growth cones are called lamellopodia filled with actin; myosin is required for contraction of cell •Growth cones grow because of tropic factors and other substances on/in a substratum

List the 4 common structural motifs in transcription regulators.

Helix-turn-helix Zinc fingers protein protruding loops Leucine zippers

What is a precursor to collagen and a mucopolysaccharide?

Heparan sulfate

What proteins are involved with packaging DNA, in reference to nucleosomes?

Histones- wrap DNA around them to forma a complex called chromatin Condensin- proteins are located at the base of the loops near the scaffold and play a role in attachment and further condensing. They also act like combs that DNA can twist around.

Give an example of a Helix- turn Helix.

Homeodomains

__________________ can activate gene expression of primary or secondary proteins (or both)

Hormones can activate gene expression of primary or secondary proteins (or both)

What disease is cause from genetic mutations leading to a deficiency of alpha iduronidase, in addition Heparan sulfate accumulates in the urine?

Hurler syndrome

In _________, the prereplicative complexes form at replication origins. In S phase, Initiation of replication includes __________ activation. ______________ form. Elongation occurs. In M phase, ___________ activation occurs and chromosomes segregate. In G1 phase, _________ and __________ activation occurs and there is assembly of new prereplicative complexes at the origins.

In G1, the prereplicative complexes form at replication origins. In S phase, Initiation of replication includes S-Cdk activation. Replication forks form. Elongation occurs. In M phase, M-Cdk activation occurs and chromosomes segregate. In G1 phase, APC/C activation and Cdk inactivation occurs and there is assembly of new prereplicative complexes at the origins.

Intermediate filaments are ropelike fibers made out of _______________________ proteins.

Intermediate filaments are ropelike fibers made out of intermediate filament proteins

Intracellular responses include _______ binding, ___________________ via kinases, removal of phosphate by ___________________, altered protein ___________________.

Intracellular responses include GTP binding, phosphorylation via kinases, removal of phosphate by phosphatases, altered protein conformation

Intrinsic Pathway of Apoptosis: §Internal response to injury or _____________ §Dependent upon release of _________________ and other proteins from __________________ which in turn activate a caspase cascade ▪Proteins bind to adaptor protein ___________ which becomes an ___________ which activates _________________ ▪Sometimes ____________ path recruits ____________ path

Intrinsic Pathway of Apoptosis: §Internal response to injury or hypoxia §Dependent upon release of cytochrome c and other proteins from mitochondria which in turn activate a caspase cascade ▪Proteins bind to adaptor protein Apaf1 which becomes an apoptosome which activates procaspases ▪Sometimes extrinsic path recruits intrinsic path

What is a syndrome that occurs because of hereditary dynein deficits?

Kartagener syndrome

Kennedy Disease is when ___________ cells (make sperm) have altered cytoskeleton and lack ______________ receptors on nucleus; Alterations in the ___________ cell cytoskeleton during development produce _____________.

Kennedy Disease is when Sertoli cells (make sperm) have altered cytoskeleton and lack androgen receptors on nucleus; Alterations in the Sertoli cell cytoskeleton during development produce infertility

__________ a protein in your fingernails, has a rigid alpha helix structure.

Keratin

What chromosome disorder has the following: Aneuploidy: Extra X chromosome Breast development, female type pubic hair pattern, small testicular size, long arms and legs, wide hips.

Klinefelter's

What syndrome is characterized by the XXY karyotype?

Klinefelter's

Ataxia telangiectasia (AT): What is the phenotype and enzyme or process affected?

Leukemia, lymphoma, gamma- ray sensitivity, genome instability ATM protein, a protein kinase activated by double- strand breaks.

Which enzyme seals together the Okazaki fragments?

Ligase

Thinking about the sarcomere, the light band is _________ only; dark band is _________ and ____________.

Light band is actin only; dark band is actin and myosin

_____________ proteins stop microtubules from sliding and allow them to bend instead, so _________________ causes bending

Linker proteins stop microtubules from sliding and allow them to bend instead, so motor action causes bending

Liver has abundant ___________ for ________________ synthesis but more sER for ________________ synthesis

Liver has abundant rER for protein synthesis but more sER for lipoprotein synthesis

Loss of Function ¢Inactivation of these genes occurs through ______________ or ________________ of sequences over a large coding region (_________) causes uncontrolled cellular proliferation because of loss of negative regulation ¢________________________________ inhibitors are one type of protein coded for by tumor suppressor genes these proteins inactivate cyclin-dependent kinases and prevent them from _________________________, thereby controlling __________________

Loss of Function ¢Inactivation of these genes occurs through mutation or deletion of sequences over a large coding region (exon) causes uncontrolled cellular proliferation because of loss of negative regulation ¢Cyclin-dependent kinase inhibitors are one type of protein coded for by tumor suppressor genes these proteins inactivate cyclin-dependent kinases and prevent them from phosphorylating, thereby controlling cell cycle

Lysozymes are examples of a protein _____________

Lysozymes are examples of a protein catalyst

Cyclin B

M Cyclin

What are the 4 phases of Eukaryotic cell cycles? Generally describe what happens in them.

M, G1, S, G2 M phase consists of mitosis (nuclear division), which is usually followed by cytokinesis (cytoplasmic division). S phase is the period of DNA replication. G1 and G2 are "gap" phases during which cells grow and do their thing.

What protein kinase complex controls all of the occurrences in early stages of mitosis?

M-Cdk

Malfunctions in __________ (tumor suppressor) or other proteins can result in ___________ (____________ does not occur as it should)

Malfunctions in p53 (tumor suppressor) or other proteins can result in cancer (apoptosis does not occur as it should)

Membrane proteins are often ________________ and there is a _____________ coat on the cell membrane

Membrane proteins are often glycosylated and there is a carbohydrate coat on the cell membrane

Membrane proteins may be associated as ________________ proteins, _______________ proteins, or ___________________ proteins

Membrane proteins may be associated as integral proteins, anchored proteins, or peripheral proteins

_______________ (made of _____________) is formed in the centrosome

Mitotic spindle (made of microtubules) is formed in the centrosome

Microtubules are formed from subunits of _____________. Alpha and beta subunits bind _______; __________ keeps it in structure, ______ can use it.

Microtubules are formed from subunits of tubulin. Alpha and beta subunits bind GTP; alpha keeps it in structure, beta can use it.

Movement in the cell starts with the extension of the ________________. Unpolymerized ___________ moves toward the ____________. Then actin _______________ occurs at ___________ end toward the protrusion. Focal adhesions on cell surface (____________) bind to substrate. Contraction on the other end of the cell is done by ____________. This allows the cell to move forward.

Movement in the cell starts with the extension of the lamellipodium. Unpolymerized actin moves toward the protrusion. Then actin polymerization occurs at plus end toward the protrusion. Focal adhesions on cell surface (integrins) bind to substrate. Contraction on the other end of the cell is done by myosin II. This allows the cell to move forward.

Multiple Sclerosis _____________ demyelinating disease, considered a__________________ ◦______________ is affected, so no nervous impulses; typically _________________ ◦Cause unknown: virus? Gene defect? Both? Cells attempting to remyelinate axons? ◦All of these stimulate the _____________ in myelin-producing cells

Multiple Sclerosis CNS demyelinating disease, considered autoimmune ◦Myelin is affected, so no nervous impulses; typically motor neurons ◦Cause unknown: virus? Gene defect? Both? Cells attempting to remyelinate axons? ◦All of these stimulate the ERSR in myelin-producing cells

Myosin: motor protein that "slides" along _______________________ for muscle contraction using ____________________.

Myosin: motor protein that "slides" along actin polymers for muscle contraction using ATP hydrolysis

Generally explain Nucleotide Excision Repair

NER: Recognition of dimer begins this repair 1. Helicase unwinds local duplex 2. Excision nuclease cleaves on both sides of damage leaving a gap of ~30 nucs 3. DNA polymerase and ligase finish job

_____________________ are important axons; these contribute to axonal diameter which is then important for the speed of ________________________.

Neurofilaments are important axons; these contribute to axonal diameter which is then important for the speed of action potential.

Actin Assembly: Newly nucleated actin filaments are attached to the sides of prexisting filaments primarily at a ______ degree angle. Filaments _____________ pushing the plasma membrane forward because of some sort of anchorage of the array behind. At a steady rate, actin filament plus ends become ___________. Behind the leading edge, the filament disassembly is performed by ___________. This allows the network to move forward as a whole.

Newly nucleated actin filaments are attached to the sides of prexisting filaments primarily at a 70 degree angle. Filaments elongate pushing the plasma membrane forward because of some sort of anchorage of the array behind. At a steady rate, actin filament plus ends become capped. Behind the leading edge, the filament disassembly is performed by cofilin. This allows the network to move forward as a whole.

What type of UV radiation can produce dimers by inducing formation of covalent linkages?

Nonionizing radiation (UVA or UVB)

Nuclear receptors are ______________ signal molecules move directly across the cell membrane These include ____________ hormones, ______ soluble vitamins, ____________ hormones

Nuclear receptors are hydrophobic signal molecules move directly across the cell membrane These include steroid hormones, fat soluble vitamins, thyroid hormones

Which receptors bind to intracellular receptor proteins which then control transcription?

Nuclear response

DNA is folded into units called _____, and a protein called _____ are at the base of chromatin loops to secure the chromosome scaffold.

Nucleosomes, condensins

What are the initiator proteins in DNA replication?

ORC are initiator proteins

Why do double stranded DNA breaks occur? What are the two methods for repair and describe them?

Occurs because of ionizing radiation issues, replication errors, oxidizing agent destruction 1. Non-homologous end joining- involves removes a set of nucleotide and ligating the strands back together. (can cause translocation or lead to nucleotide deletion) 2. Homologous recombination- Occurs after replication when there is a nearby daughter DNA duplex that can serve as a template for repair. ( can cause loss of heterozygosity and can cause deletion/ alteration of repair proteins that can result in cancer. ex: Brca 1 and 2

When does depurination occur?

Occurs when the bond connecting a purine to its deoxyribose sugar is broken by a molecule of water, resulting in a purine- free nucleotide that cannot act as a template during DNA replication.

Benign

Of tumors, self- limiting in growth, and noninvasive.

Off to the Golgi... ◦Those that go out of the ER to further processing in the Golgi are mostly processed by addition of ___________________ ◦This protein __________________ occurs at the ______________ group of an________________ in the protein >> "______-linked" >> Complex process with end result being removal of _____________ and glucoses ("_________________") >> Important for transmembrane proteins on _____________ side for cell-cell interaction ◦Oligosaccharide tags on 90% of ________________ and are markers of protein _______________.

Off to the Golgi... ◦Those that go out of the ER to further processing in the Golgi are mostly processed by addition of oligosaccharides ◦This protein glycosylation occurs at the amine group of an asparagine in the protein ◦"N-linked" ◦Complex process with end result being removal of mannose and glucoses ("trimming") ◦Important for transmembrane proteins on extracellular side for cell-cell interaction ◦Oligosaccharide tags on 90% of glycoproteins and are markers of protein folding

Once a cell membrane receptor has bound an extracellular signal, a second message is sent within the cell by __________________

Once a cell membrane receptor has bound an extracellular signal, a second message is sent within the cell by intracellular signaling proteins

Oncogenes ¢Oncogenes originate from ___________________ that encode protein products that control cell ____________ and __________________. >When activated by ______________, these act as dominant _______________ mutations that lead to the deregulation of cell cycle control >>A _______________-promoting effect >>_____________, K-ras, Wnt-3, her-2/neu, _______________

Oncogenes ¢Oncogenes originate from proto-oncogenes that encode protein products that control cell growth and differentiation >When activated by mutation, these act as dominant gain-of-function mutations that lead to the deregulation of cell cycle control >>A growth-promoting effect >>Myc, K-ras, Wnt-3, her-2/neu, Cyclin E

Organelle structure is highly specialized for ______________ synthesis, ______________ and transport, energy ______________, protein __________________.

Organelle structure is highly specialized for protein synthesis, segregation and transport, energy production, protein degradation

Organelles membranes require _______________ and are __________________.

Organelles membrane require transporters and are self replicating.

What is the mitochondrion? What is it functions?

Organelles that generate most of the cell's supply of ATP Other functions include free radical generation, apoptosis control, as well as cell growth and cell cycle regulation

What are 3 major components necessary for chromosomal function?

Origins for the initiation of DNA replication Centromere Two telomeres at both ends (prevents the chromosome from being degraded by DNA repair enzymes)

Other treatments for cancers ¢______________ therapy ¢_______________ transplants ¢_________________ ¢________________ therapy ¢The ________ initiative ________________ mutations of __________ genes are drivers of human cancers and are often seen as an initiating event _____________ mutations are common in specific cancer types >> G12D: __________ cancer mutation >> G12C: __________ cancer mutation _____________ co-mutates with KRAS (more likely to be altered where ____________ was mutated

Other treatments for cancers ¢Gene therapy ¢Stem cell transplants ¢Surgery ¢Radiation therapy ¢The RAS initiative Missense mutations of RAS genes are drivers of human cancers and are often seen as an initiating event KRAS mutations are common in specific cancer types ¢G12D: pancreatic cancer mutation ¢G12C: lung cancer mutation TP53 co-mutates with KRAS (more likely to be altered where KRAS was mutated

____________________ (self-phosphorylating): multipass proteins that maintain ionic gradients

P-type pumps (self-phosphorylating): multipass proteins that maintain ionic gradients

__________: Guardian of the Genome ¢Tumor _________________ gene, ________________ gene ¢Only functions in certain circumstances, limiting the harm done by DNA damage Can set ____________________ in motion Stops cell _______________ and cell ______________ Induces _________________ of p21 Loss of___________ promotes cancer by: >>Allowing DNA-damaged cells to ____________ >>Allows damaged cells to escape ________________ >>Leads to genetic ______________ >>Makes cells ______________ to anti-cancer drugs >>Guardian of the Genome

P53: Guardian of the Genome ¢Tumor suppressor gene, DNA repair gene ¢Only functions in certain circumstances, limiting the harm done by DNA damage Can set apoptosis in motion Stops cell division and cell cycle Induces transcription of p21 Loss of p53 promotes cancer by: >>Allowing DNA-damaged cells to divide >>Allows damaged cells to escape apoptosis >>Leads to genetic instability >>Makes cells resistant to anti-cancer drugs >>Guardian of the Genome

________: Guardian of the Genome: >If cellular DNA is damaged, p53 (________________) accumulates, activates other proteins which in turn trigger the_______________ pathway

P53: Guardian of the Genome: ¡If cellular DNA is damaged, p53 (tumor suppressor) accumulates, activates other proteins which in turn trigger the intrinsic pathway

•All cells have a nonmotile cilia called the ____________________.

PRIMARY CILIUM

Prion =___________________ and __________ ________

PRoteinaceous and Infectious Virion

_____________ is a novel small-molecular agent that makes ribosomes become less sensitive to, or possibly ignore stop ____________. This is particularly beneficial in genetic disorders where the _________ sequence of an implicated, non-functioning protein contains a premature stop codon. However, it is not equally effective with every stop codon, working best on the sequence '_________'

PTC124 is a novel small-molecular agent that makes ribosomes become less sensitive to, or possibly ignore stop codons. This is particularly beneficial in genetic disorders where the mRNA sequence of an implicated, non-functioning protein contains a premature stop codon. However, it is not equally effective with every stop codon, working best on the sequence 'UGA'

___________________: signals (local mediators) are released but affect only targets in the vicinity __________________: cells produce signals that they respond to themselves An example is ________________

Paracrine Signaling: signals (local mediators) are released but affect only targets in the vicinity Autocrine signals: cells produce signals that they respond to themselves Cancer cells

What type of transport uses a concentration gradient? What is the gradient called when there is electrical potential and concentration gradient involved?

Passive transport electrochemical gradient

What are the types of transport?

Passive transport of uncharged molecules is dependent on a downhill process called a concentration gradient Active transport is an uphill process, requiring transporters to be linked to energy

Family B: ________: forms complex with pol subunits to act as a primase (synthesizing an RNA primer) then elongates that primer for ~20 nucleotides. starts the process ________: Exonuclease function. likely involved in leading and lagging strand synthesis. takes over from Pol α ________: Exonuclease, not clear if involved in leading and lagging strand synthesis

Pol α, Pol δ, Pol ε

Family X: ______: DNA repair (base-excision and gap-filling) _______ and ______: Non-homologous end-joining repair

Pol β, Pol λ and μ

Family A: _________: Replicates and repairs mitochondrial DNA

Pol γ

Family Y: ______,_____, and _______ : translesion synthesis, not real good and will replicate through damaged DNA but useful

Pol η, ι, κ

______________ molecules (sugars, nucleotides, ions, etc.) use membrane transport proteins

Polar molecules (sugars, nucleotides, ions, etc.) use membrane transport proteins

Post-translational translocation (not an _________ process) ◦_______________ ribosomes complete protein synthesis and release prior to the protein being __________________ to a mitochondrial membrane, nuclear membrane, etc.

Post-translational translocation (not an ER process) ◦Free ribosomes complete protein synthesis and release prior to the protein being translocated to a mitochondrial membrane, nuclear membrane, etc.

Proteins that do not remain in the ER are ___________________ in the __________________________

Proteins that do not remain in the ER are glycosylated in the Golgi apparatus

What are key differences between prokaryotes and eukaryotes including structure and function?

Prokaryotes have no nucleus or mitochondria, unicellular, and are mostly ribosomes and DNA, have a cell wall and a plasma membrane. Eukaryotes have a larger size and more elaborate structure, bigger genomes, DNA in a nucleus, a complex cytoskeleton, and ability to phagocytose things.

Protein processing in Golgi compartments: From the ER, proteins are sorted in the _____________________ and oligosaccharides on __________________ proteins are phosphorylated. In the cis cisterna, ______________ is removed. In the _________________, mannose is remove and N-acetylglucosamine is added. In the trans cisterna, ________________ is added and __________________ acid (___________) is added. In the trans Golgi, ________________ of tyrosines and ___________________ occurs and proteins are sorted according to their final destination.

Protein processing in Golgi compartments: From the ER, proteins are sorted in the cis Golgi network and oligosaccharides on lysosomal proteins are phosphorylated. In the cis cisterna, mannose is removed. In the medial cisterna, mannose is remove and N-acetylglucosamine is added. In the trans cisterna, galactose is added and N-acetylneuraminic acid (sialic acid) is added. In the trans Golgi, sulfation of tyrosines and carbohydrates occurs and proteins are sorted according to their final destination.

(the nonhelical loops of the proteins, flexible)

Protein protruding loops

What are examples for extracellular signals?

Proteins Amino acids Steroids, steroid hormones Nitric oxide

Proteins in intrinsic pathway: >____________ proteins required for intrinsic pathway §These are considered ____________ of cell death as some are ______________ and others are __________________ ▪Pro-apoptotic proteins are __________(Bak and Bax) and __________ ▪________________ proteins are Bcl2 and Bcl-XL ▪These proteins are kind of like "__________________" as they are located on ________________ membranes ▪_____________ first, then _________ anti-apoptotics, then _____________ proteins

Proteins in intrinsic pathway: >Bcl2 proteins required for intrinsic pathway §These are considered regulators of cell death as some are pro-apoptotic and others are anti-apoptotic ▪Pro-apoptotic proteins are BH123 (Bak and Bax) and BH3-only ▪Anti-apoptotic proteins are Bcl2 and Bcl-XL ▪These proteins are kind of like "membrane guardians" as they are located on organelle membranes ▪BH3-only first, then Bcl2 anti-apoptotics, then effector proteins

Proteoglycan assembly proteoglycans ◦They are assembled in the _____________ ◦________________ transferase enzymes link oligos to _____________ groups of certain amino acids in a protein backbone; addition of ______________ chains ◦Proteoglycans are important in the ______________________

Proteoglycan assembly ◦They are assembled in the Golgi ◦Glycosyl transferase enzymes link oligos to hydroxyl groups of certain amino acids in a protein backbone; addition of GAG chains ◦Proteoglycans are important in the extracellular matrix

__________________ (Molecule consisting glycosaminoglycan chain(s) attached to a core protein) are synthesized in the Golgi

Proteoglycans (Molecule consisting glycosaminoglycan chain(s) attached to a core protein) are synthesized in the Golgi

Proto-Oncogenes/Oncogenes: ¢Proto-oncogenes: necessary for normal cellular ________________; originally obtained from ________________ ¢Proto-oncogenes can become "_______________" typically by ___________________ to become oncogenes ¢These are like the accelerator on a bus, with the destination being __________________!

Proto-Oncogenes/Oncogenes ¢Proto-oncogenes: necessary for normal cellular proliferation; originally obtained from viruses ¢Proto-oncogenes can become "activated" typically by point mutation to become oncogenes ¢These are like the accelerator on a bus, with the destination being cell division!

What are the 3 categories of Cancer-Critical Genes?

Proto-oncogenes/oncogenes Tumor suppressor genes DNA maintenance genes

Proto-onocogenes normally promote cell division but become over-activated as _____________ in cancer

Proto-onocogenes normally promote cell division but become over-activated as oncogenes in cancer

What is the role of histones in cells?

Provide positively charges core that DNA wraps tightly around due to electrostatic interaction between the negative charges of the DNA sugar phosphate backbone (1st level of organization, and packages the DNA into the nucleosome DNA wound around the histone core) Chromatin are formed after the DNA is tightly wrapped around the histone cores. Nucleosomes are the basic unit of chromatins! When unfolded it looks like a string of beads, the string is DNA and each bead is a nucleosome core particle! The function is to compress DNA into a compact unit that will take up less space within the nucleus

Purpose of the Golgi Why do proteins even need to go through the Golgi? >> Secondary _________________ processing: ______________________ added in ER, further glycosylation and _________________ occurs in Golgi with different enzymes at each region of Golgi (_______ and _________________ formation) >> ___________________ necessary for protein folding, resistance to _______________ digestion, sugars can be recognized by _______________ important during development and cell-cell adhesion

Purpose of the Golgi Why do proteins even need to go through the Golgi? >> Secondary oligosaccharide processing: oligosaccharides added in ER, further glycosylation and phosphorylation occurs in Golgi with different enzymes at each region of Golgi (mucins and proteoglycan formation) >> Glycosylation necessary for protein folding, resistance to proteolytic digestion, sugars can be recognized by lectins important during development and cell-cell adhesion

RNA Conformation RNA is also a _____________, but it is a single-stranded one. Because of its flexibility, it can fold back on itself and complementary sequences can bind, forming a ______________ molecule. Other sequences in the RNA strand can recognize different molecules, too.

RNA Conformation RNA is also a polymer, but it is a single-stranded one. Because of its flexibility, it can fold back on itself and complementary sequences can bind, forming a folded molecule. Other sequences in the RNA strand can recognize different molecules, too.

cancer stem cells

Rare cancer cells capable of dividing indefinitely.

BRCA 1 and BRCA 2; What is the enzyme or process affected?

Repair by homologous recombination

_____________ only occurs during the S phase of interphase just before g2 repair and M mitosis.

Replication

__________________________: rare disorders involving impaired ribosome biogenesis and function; mutations affect _______________and protein synthesis: o Alterations in genes encoding ribosomal ______________ >> Congenital mutation in RPS19 causes hypoplastic ____________________ (__________________________ anemia) and bone marrow failure o Alterations in genes involved in ribosomal ___________________ · Congenital mutation produces _____________ syndrome similar to DB anemia · Others include cartilage hair hypoplasia, ______________________ syndrome o Ribosomal function abnormalities activate _________ pathway · ________-syndrome is a deletion of entire __- arm of chromo ____ presents w/ severe macrocytic anemia

Ribosomopathies: rare disorders involving impaired ribosome biogenesis and function; mutations affect translation and protein synthesis: o Alterations in genes encoding ribosomal proteins >> Congenital mutation in RPS19 causes hypoplastic macrocytic anemia (Diamond Blackfan anemia) and bone marrow failure o Alterations in genes involved in ribosomal biogenesis · Congenital mutation produces myelodysplastic syndrome similar to DB anemia · Others include cartilage hair hypoplasia, Treacher-Collins syndrome o Ribosomal function abnormalities activate p53 pathway · 5q-syndrome is a deletion of entire q arm of chromo 5 presents w/ severe macrocytic anemia

__________________ is studded with ribosomes, located in all eukaryotic cells

Rough ER is studded with ribosomes, located in all eukaryotic cells

During which phase of the cell cycle does replication occur?

S phase

What phase does DNA replication occur?

S phase

S-Cdk presence and deconstruction of pre-RC bring on the ___________________ complex and _________________ of ORC

S-Cdk presence and deconstruction of pre-RC bring on the pre-initiation complexes and phosphorylation of ORC

Second messenger signals such as ________ and calcium or diacylglycerol pass along the signal to ____________. Effectors are like "_____________________" with on and off properties

Second messenger signals such as cAMP and calcium or diacylglycerol pass along the signal to effectors Effectors are like "molecular switches" with on and off properties

Signal Recognition Particles A guide is needed to move signal sequence to ______________________ ◦SRP guides ____________________ to ER translocator and SRP receptor. ____________ has a signal sequence binding site lined with ______________ (flexible) so it can accommodate many signal sequences. ◦SRP contains an ___________ and six ______________ subunits. ◦Rod-like, wraps around the __________________ subunit. One end binds to the signal sequence, the other blocks the__________ site so translation is halted.

Signal Recognition Particles A guide is needed to move signal sequence to translocator ◦SRP guides signal sequence to ER translocator and SRP receptor. SRP has a signal sequence binding site lined with methionine (flexible) so it can accommodate many signal sequences. ◦SRP contains an RNA and six protein subunits. ◦Rod-like, wraps around the large ribosomal subunit. One end binds to the signal sequence, the other blocks the E site so translation is halted.

_________________ Sequences: First discovered in proteins imported into the __________ ◦_____________________ (destined for ER, other organelle, or cell membrane) and water soluble proteins (secreted or stay within an organelle); both have signal sequence ◦Used in both __________________ translocation and ____________________ translocation Signal sequence is a short sequence of amino acids at the ______-terminal that direct secreted protein to the ER...it is then cleaved off by a ________________________ ◦The sequence is different for different polypeptides, but contains several _____________ (polar or nonpolar) AAs

Signal Sequences: First discovered in proteins imported into the rER ◦Transmembrane (destined for ER, other organelle, or cell membrane) and water soluble proteins (secreted or stay within an organelle); both have signal sequence ◦Used in both co-translational translocation and post-translational translocation Signal sequence is a short sequence of amino acids at the N-terminal that direct secreted protein to the ER...it is then cleaved off by a signal peptidase ◦The sequence is different for different polypeptides, but contains several nonpolar AAs

When Cell Communication Goes Wrong: What diseases occur? Signals are lost? Cell signal does not reach target? Target cell does not respond? Too much signal?

Signals are lost Diabetes type I Loss of immune protection Cell signal does not reach target Multiple sclerosis Target cell does not respond Diabetes type 2 Too much signal Stroke with release of glutamate in brain

What is Hurler syndrome and what accumulate in the urine?

Skeletal and collagen involvement: Group of disorders involving genetic mutations leading to a deficiency of alpha iduronidase. results in lack of collagen formation in several systems death occurs by age 8. Heparan sulfate (precursor to collagen and a mucopolysaccharide) accumulates in urine

Xeroderma pigmentosum: What is the phenotype and enzyme or process affected?

Skin cancer, UV sensitivity, neurological abnormalities Nucleotide excision repair.

_________________ ER has no ribosomes and is located in cells that specialize in ____________ metabolism, such as cells that synthesize steroid hormones from ____________________.

Smooth ER has no ribosomes and is located in cells that specialize in lipid metabolism, such as cells that synthesize steroid hormones from cholesterol

_________________ is the disease where the neural tube closure requires numerous cellular events based on cell migration. What is recommended to pregnant to women to prevent this?

Spina Bifida is the disease where the neural tube closure requires numerous cellular events based on cell migration. Folic acid

which disorder is the result of a dysfunction in cell migration?

Spina bifida

Steps in the Process: Morphological changes §Membrane ____________ or shrinkage and ______________ §_________________ collapse §Disassembly of _________________________ §Chromatin ___________________ Chemical changes §Cell surface is altered for ________________ recognition §Intracellular proteins act as _____________ and ____________ of cell destroyers

Steps in the Process: Morphological changes §Membrane blebbing or shrinkage and condensation §Cytoskeletal collapse §Disassembly of nuclear envelope §Chromatin fragmentation Chemical changes §Cell surface is altered for phagocytic recognition §Intracellular proteins act as signals and activators of cell destroyers

What are the two types of long range signalers?

Synaptic and Endocrine

Structure of Proteoglycans > ___________________ serves as a backbone > Link proteins connect ___________ proteins > From there are branching ____________________________________

Structure of Proteoglycans > Hyaluronic acid serves as a backbone >Link proteins connect core proteins > From there are branching O- and N-linked oligosaccharides

Survival Factors: > Cells require ____________ signals from other cells to avoid _____________ §Cells with no signals cannot import _____________ and eat themselves (______________) but eventually starve to death (this is not ________________)

Survival Factors: >Cells require extracellular signals from other cells to avoid apoptosis §Cells with no signals cannot import nutrients and eat themselves (autophagy) but eventually starve to death (this is not apoptosis)

Survival Pathways: 1. Increased production of anti-apoptotic ________ family protein. 2. Inactivation of pro-apoptotic ____________ protein, which activates BCL2. 3. Inactivation of anti-IAPs. Survival factors activate the __________________ pathway, inactivating Hid by _____________. This produces IAPs, blocking _________________.

Survival Pathways: 1. Increased production of anti-apoptotic Bcl2 family protein. 2. Inactivation of pro-apoptotic BH3-only protein, which activates BCL2. 3. Inactivation of anti-IAPs. Survival factors activate the MAP kinase pathway, inactivating Hid by phosphorylation. This produces IAPs, blocking apoptosis.

__________________: Nervous system neurons with long axons that release chemical neurotransmitters onto post-synaptic sites (synapse is the locale of release); these sites then have an electrical reaction (____________________) based upon the type

Synaptic: Nervous system neurons with long axons that release chemical neurotransmitters onto post-synaptic sites (synapse is the locale of release); these sites then have an electrical reaction (action potential) based upon the type

What is the main function of DNA polymerase alpha?

Synthesizes RNA primer

Targeted Molecular Therapies ¢Part of "______________________" using individual's genome and _______________ to treat cancer ¢These are drugs or other substances that block _______________ and spread of cancer by interfering with "______________" >> NOT standard chemo (which acts on all rapidly _____________ cells), because they act on specific _______________ targets >> Considered ________________ (blocks cell proliferation), not ________________ (kills tumor cells)

Targeted Molecular Therapies ¢Part of "precision medicine" using individual's genome and proteome to treat cancer ¢These are drugs or other substances that block growth and spread of cancer by interfering with "targets" >> NOT standard chemo (which acts on all rapidly dividing cells), because they act on specific molecular targets >> Considered cyostatic (blocks cell proliferation), not cytotoxic (kills tumor cells)

______________ are the most interesting. These repeated sequences (GGTTAGGTTA...) form the ends of a chromosome and protect the chromosome from being eaten by ___________________.

Telomeres, DNA repair genes

What is the final stage of mitosis?

Telophase

Some proteins combine several alpha helices as, while others combine several helices and pleated sheets. The interaction and combination of different primary and secondary structures form a ___________ structure

Tertiary

The ER is an interconnected network of ______________, ___________, and ________________.

The ER is an interconnected network of tubules, vesicles, and cisternae

The _________________ processes proteins with additions of carbohydrates, also forms lysosomes and endosomes

The Golgi processes proteins with additions of carbohydrates, also forms lysosomes and endosomes

The actin monomer has a nucelotide (either _______ or ______) bound in a deep cleft in the center of the molecule. Arrangement of monomers in a filament consisting of ______ protofilaments, held together by lateral contacts, which wind around each other as two _____________ strands of a helix. All subunits within the filament have the same orientation.

The actin monomer has a nucelotide (either ATP or ADP) bound ina deep cleft in the center fo the molecule. Arrangment of monomers in a filament consisting of two protofilaments, held together by lateral contacts, which wind aorund each other as two parallel strands of a helix. All subunits within the filament have the same orientation.

The activation of APC/C by _________ (protein) leads to the ____________ (process) and destruction of __________, which normally holds separase in an inactive state. The destruction of this protein allows separase to cleave ________, a subunit of the __________ complex holding the sister chromatids together. The pulling forces of the ______________ then pull the sister chromatids apart. In animal cells, phosphorylation by Cdks also inhibits __________. Thus Cdk inactivation in anaphase (resulting from cyclin destruction ) also promotes __________ activation by allowing its _________________ of Cdk.

The activation of APC/C by Cdc20 leads to the ubiquitylation and destruction of securin, which normally holds separase in an inactive state. The destruction of securin allows separase to cleave Scc1, a subunit of the cohesin complex holding the sister chromatids together. The pulling forces of the mitotic spindle then pull the sister chromatids apart. In animal cells, phosphorylation by Cdks also inhibits separase. Thus Cdk inactivation in anaphase (resulting from cyclin destruction ) also promotes separase activation by allowing its dephorphorylation of Cdk.

The ___________ microtubules are attached to the surface of the centrosome. The ____________ microtubules attach to centrosome and chromosomes to pull apart ________________. The ___________ microtubules help to push the daughter cells apart. _____________ facilitate the process.

The astral microtubules are attached to the surface of the centrosome. The kinetochore microtubules attach to centrosome and chromosomes to pull apart sister chromatids. The interpolar microtubules help to push the daughter cells apart. Motor proteins facilitate the process.

The ________________ can be smooth or rough

The endoplasmic reticulum can be smooth or rough

The sarcomere has a centrally located _____________ of ____________ (thick filaments). On either side there are ________ (thin filaments), all in parallel. Interspersed are coiled _________ proteins. On the ________ end of each actin section is a __________. The ____________, central __________, and two units of _______________ on either side make up one sarcomere.

The sarcomere has a centrally located M line of myosin (thick filaments). On either side there are actin (thin filaments), all in parallel. Interspersed are coiled titin proteins. On the plus end of each actin section is a Z disc. The M line, central myosin, and two units of actin filaments on either side make up one sarcomere.

metastasis

The spread of cancer cells from their site of origin to other sites in the body.

There are 3 classes of cell-surface receptors: What are they?

There are 3 classes of cell-surface receptors: ion-gated channels, G-protein coupled receptors, and enzyme coupled receptors

There are 4 types of signaling: what are they?

There are 4 types of signaling: contact-dependent, paracrine, synaptic, and endocrine

A triploidy means:

There are three copies of every chromosome

A trisomy means:

There are three copies of one chromosome.

Think about Intrinsic Pathway: An apoptotic stimulus activates ___________ protein and inactivates the ______________ BCL2 family protein. The ___________ proteins then aggregate allowing release of ____________________ proteins from the mitochondria, including _____________________.

Think about Intrinsic Pathway: An apoptotic stimulus activates BH3-only protein and inactivates the anti-apoptotic BCL2 family protein.The BCL2 proteins then aggregate allowing release of intermembrane proteins from the mitochondria, including cytochrome C.

What is the role of topoisomerase?

To prevent supercoiling and tangling of DNA

Translocation process SRP then binds to SRP ____________, an _________________ membrane protein on ER membrane. Ribosome with polypeptide attaches to an ______________________ (Sec 61 complex) and peptide is completed within ER ___________________

Translocation process SRP then binds to SRP receptor, an integral membrane protein on ER membrane. Ribosome with polypeptide attaches to an aqueous protein translocator (Sec 61 complex) and peptide is completed within ER cistern

_________________________ proteins that are single-pass (pass through the membrane only once) alpha helices are different from water soluble proteins (stay in __________________). _______________ is the same, but there is a hydrophobic segment in the peptide chain that is a ____________________ that anchors protein in __________________.

Transmembrane proteins that are single-pass (pass through the membrane only once) alpha helices are different from water soluble proteins (stay in cytosol). Translocation is the same, but there is a hydrophobic segment in the peptide chain that is a stop-transfer signal that anchors protein in membrane

Transport vesicles ◦From specialized ____________ regions of membranes ◦Coats include _____________ (from Golgi and plasma membrane), __________ and ___________ (from ER and Golgi)

Transport vesicles ◦From specialized coated regions of membranes ◦Coats include clathrin (from Golgi and plasma membrane), COP-I and COP II (from ER and Golgi)

Transport _______________ are used to move particles from compartment to compartment

Transport vesicles are used to move particles from compartment to compartment

What makes up 40% of DNA in humans and are referred to as the "jumping genes", why are they called this?

Transposons, because they are made up of mobile genetic elements

Tumor Progression In Cancer: At least ___ mutations are required for onset of clinically observable tumors 1._____________________: extra copies of a single gene are transcribed 2.__________ mutations (genes are truncated) 3.____________: loss of a sequence of nucleotides within an exon or splice site 3._________________: in Ig-producing cells (__ and __) can produce massive clonal populations 4._____________: replacement of a single nucleotide

Tumor Progression In Cancer: At least 5 mutations are required for onset of clinically observable tumors 1.Gene amplification: extra copies of a single gene are transcribed 2.Nonsense mutations 3.Gene deletion: loss of a sequence of nucleotides within an exon or splice site 3.Gene rearrangements: in Ig-producing cells (T and B) can produce massive clonal populations 4.Point mutations: replacement of a single nucleotide

Tumor _______________________ Genes: ¢Encode for _______________ products that _______________ tumor formation by controlling cell _______________. >> _________________________ mutations result in inactivation of the tumor _____________________ and can lead to uncontrolled cellular _________________ >> ____________, BRCA1, E3 ______________________, RB, p16ink4a ¢These are like the brakes on the bus!

Tumor Suppressor Genes: ¢Encode for protein products that suppress tumor formation by controlling cell growth >> Loss-of-function mutations result in inactivation of the tumor suppressor protein and can lead to uncontrolled cellular proliferation >> p53, BRCA1, E3 ubiquitin protein, RB, p16ink4a ¢These are like the brakes on the bus!

Tumor cells may enter the __________________ directly by crossing the wall of a ________________________, or more commonly by crossing the wall of a _____________ _____________ that ultimately discharges its contents (lymph) into the bloodstream. Tumor cells that have entered a ________________ vessel often become trapped in _____________________ along the way, giving rise to lymph node metastases. Studies in animals show that typically far fewer than one in every thousand ______________________ tumor cells that enter the bloodstream will colonize a new _________________ so as to produce a detectable tumor at a ___________.

Tumor cells may enter the bloodstream directly by crossing the wall of a blood vessel, as diagrammed here, or more commonly by crossing the wall of a lymphatic vessel that ultimately discharges its contents (lymph) into the bloodstream. Tumor cells that have entered a lymphatic vessel often become trapped in lymph nodes along the way, giving rise to lymph node metastases. Studies in animals show that typically far fewer than one in every thousand malignant tumor cells that enter the bloodstream will colonize a new tissue so as to produce a detectable tumor at a new site.

Tumors Induce _____________________: Cell aggregates need oxygen to survive; without oxygen, __________ sets in Hypoxia activates an ________________ switch that increases _________________ Factor (a gene regulatory protein) that activates _____________ of genes that encode _______________ that attract _________________ cells (via VEGF) and formation of new _________________________. ____________________ may function this way

Tumors Induce Angiogenesis: Cell aggregates need oxygen to survive; without oxygen, hypoxia sets in Hypoxia activates an angiogenic switch that increases Hypoxia-inducible Factor (a gene regulatory protein) that activates transcription of genes that encode proteins that attract endothelial cells (via VEGF) and formation of new blood vessels Tumors may function this way

Tumors are ____________ ¢_____________ are comprised of genetically identical cells and are "______________" in nature; a single aberrant cell starts it all ¢Alterations in cellular DNA accumulate over time in succeeding generations of ________________ cells (__________________) ¢Daughter cells with several __________________ replace the cells previously comprising the ________________

Tumors are Clones ¢Tumors are comprised of genetically identical cells and are "clonal" in nature; a single aberrant cell starts it all ¢Alterations in cellular DNA accumulate over time in succeeding generations of daughter cells (clonal expansion) ¢Daughter cells with several mutations replace the cells previously comprising the tumor

Tumors consist of many cell types including ____________ cells, ______________ cells, pericytes, __________________, and inflammatory _________________ cells. ___________________ among these and other cell types plays an important part in tumor development. Only the ______________ cells are thought to be genetically abnormal in a tumor.

Tumors consist of many cell types including cancer cells, endothelial cells, pericytes, fibroblasts, and inflammatory white blood cells. Communication among these and other cell types plays an important part in tumor development. Only the cancer cells are thought to be genetically abnormal in a tumor.

Tumors need to recruit nutrients by forming a ____________________

Tumors need to recruit nutrients by forming a blood supply

What chromosome disorder has the following: Aneuploidy: One X, monosomy

Turner's

Types of available therapies ¢Standard chemotherapy to break down cells' ____________________ so no cell __________________ ¢Standard chemo plus _______________ therapy ¢Targeted therapy only if _____________ does NOT work >> ________________ therapies: stop growth of hormone-sensitive tumors for _____________ and ____________ cancers >> ___________________________ inhibitors: blocks signal transduction in continuously dividing cells (________________®) >> ________________________________: modifies proteins that are involved in gene expression (e.g. regulatory proteins) >> _________________________: get around cancer's ability to avoid apoptosis >> ________________________________: targets proteins that stimulate new blood vessel growth >> ___________________: use of monoclonal antibodies that bind to specific molecules on cell surface and use immune destruction to kill cell >> ______________________ attached to toxin

Types of available therapies ¢Standard chemotherapy to break down cells' cytoskeleton so no cell division ¢Standard chemo plus targeted therapy ¢Targeted therapy only if chemo does NOT work >> Hormone therapies: stop growth of hormone-sensitive tumors for breast and prostate cancers >> Signal transduction inhibitors: blocks signal transduction in continuously dividing cells (Tarceva®) >> Gene expression modulators: modifies proteins that are involved in gene expression (e.g. regulatory proteins) >> Apoptosis inducers: get around cancer's ability to avoid apoptosis >> Angionenesis inhibitors: targets proteins that stimulate new blood vessel growth >> Immunotherapy: use of monoclonal antibodies that bind to specific molecules on cell surface and use immune destruction to kill cell >> Monoclonal antibody attached to toxin

What happened to DNA when exposed to UV ?

UV exposure: forms pyrimidine dimers via covalent linkage between two bases

XP variant: What is the phenotype and enzyme or process affected?

UV sensitivity, skin cancer Translesion synthesis by DNA polymerase ν

Cockayne syndrome: What is the phenotype and enzyme or process affected?

UV sensitivity; developmental abnormalities Coupling of nucleotide excision repair to transcription.

Vesicles to the Golgi How do transport vesicles make it to the Golgi? ◦Vesicles shed the ___________ coat and ________ with each other ◦"___________________" utilizes ___________ proteins (transmembrane proteins that catalyze membrane fusion reactions)...a ____________ and a _____________ are required to force lipid bilayers closed and expel water ◦Structures form that are called "__________________________" which are pulled along ___________________ to the Golgi cis face

Vesicles to the Golgi How do transport vesicles make it to the Golgi? ◦Vesicles shed the COPII coat and fuse with each other ◦"Homotypic fusion" utilizes SNARE proteins (transmembrane proteins that catalyze membrane fusion reactions)...a t-SNARE and a v-SNARE are required to force lipid bilayers closed and expel water ◦Structures form that are called "vesicular tubular clusters" which are pulled along microtubules to the Golgi cis face

Vesicular fusion complexes form when multiple ____________________ combine on way to Golgi, facilitated by _____________ proteins

Vesicular fusion complexes form when multiple vesicles combine on way to Golgi, facilitated by SNARE proteins

What are the functions of the ER? ◦Protein __________________ ◦Folding and transport of ________________ to be used in some cell membrane (e.g. transmembrane _____________ and other integral membrane proteins) or to be _______________ from the cell (e.g. digestive enzymes) ◦Rebuilding _______________ after _________________ ◦N-linked __________________ of proteins ◦Production and storage of ______________, _____________, and other macromolecules (sER in part) ◦Sequestration of ______________ (sER)

What are the functions of the ER? ◦Protein translation ◦Folding and transport of proteins to be used in some cell membrane (e.g. transmembrane receptors and other integral membrane proteins) or to be exocytosed from the cell (e.g. digestive enzymes) ◦Rebuilding nuclear envelope after cytokinesis ◦N-linked glycosolation of proteins ◦Production and storage of glycogen, steroids, and other macromolecules (sER in part) ◦Sequestration of calcium (sER)

•Spontaneous oxidative destruction: reactive oxygen radicals or chemical exposure cause base damage (red arrows) •Uncontrolled methylation (green arrows) •Hydrolytic attack (blue arrows)

What is going on in this image? What do each of the colored arrows indicate?

What is a nonsense mutation?

When a mutation creates a premature stop codon causing a truncated, usually nonfunctioning protein

Why apoptosis? > Development: more cells than needed are made just in case then have to be ______________________ > __________________ during development for abnormal cells > Organ/tissue ______________ > _________________ of short-lived cell supply > ______________ damage > Elimination of bad ____________________ cells, unneeded activated _____________________.

Why apoptosis? > Development: more cells than needed are made just in case then have to be eliminated > Quality control during development for abnormal cells > Organ/tissue sculpting > Maintenance of short-lived cell supply > Organelle damage > Elimination of bad immune system cells, unneeded activated lymphocytes

What binds to DNA binding proteins with a zinc moiety? What conformations can it hold together?

Zinc fingers Zinc can hold alpha helix and beta sheet together.

What disease is located on the gene map 13q33?

XP- A defect in one of several DNA repair genes is expressed as a dysfunctional repair enzyme...this is heritable as the mutation occurs in the germ line. Skin cell mutations persist, resulting in tumors.

DNA binding proteins with a zinc moiety (has zinc areas that condense the protein together to give it a structural area which allows it to bind to the alpha helix)

Zinc Fingers:

Define structural motif.

a common structure used by regulator proteins that allows for binding to the double helix.

carcinogen

a substance capable of causing cancer in living tissue.

Which molecule is active in preparation for DNA replication, before polymerase is copying the DNA strands? a. G1/S Cdk b. M Cdk c. Q Cdk d. AP/C

a. G1/S Cdk

What statement is NOT true regarding P-type ATPase transporters and ABC transporters? a. The CTFR protein is an example of a P-Type ATPase b. P-type usually transport ions, ABCs usually transport small molecules c. The pump that returns calcium to the sarcoplasmic reticulum is a P-type ATPase d. P-type have 1 ATP binding domain, ABC has 2 ATP binding domains

a. The CTFR protein is an example of a P-Type ATPase this is not true because CTFR is an ABC transporter!

In step 6 of the ways of gene regulation, what post translational modifications are used?

acetylation, phosphorylation, ubiquitination

positive regulators = ?? negative regulators = ??

activators repressors

Abnormally folded proteins can result in many different diseases, because they form _______ due to the loss of cellular quality control. Normal proteins that begin to form these will eventually lead to the formation of __________ fibrils. Which organ is particularly sensitive to this? These _______________ filament proteins are ____________ resistant.

aggregates amyloid brain cross-beta, protease

Filament nucleation is process of initial __________________.

aggregation

Two regular folding patterns caused by hydrogen bonding are found in parts of proteins: the ___________ and the ______________. What structure is this statement talking about?

alpha helix, beta sheet secondary structure

What is the secondary structure of a protein?

amino acids interact with each other to form basic structure

-All known prions induce the formation of __________

amyloid

How can cell membrane fluidity be increased? a. increase the number of cholesterol molecules b. increase the unsaturated double bonds in phospholipid tails c. increase the number of linear single bonded hydrophobic tails d. increase the amount of hydrophobic molecules on the surface

answer b

-Non-coding RNAs:

any RNA that is produced and doesn't go on to be translated to protein

Controlled cellular suicide in animal cells mostly through _________________ but not always; others include.... list them.

apoptosis §Autophagy §"Non-apoptotic programmed cell death" "caspase-independent..." §Anoikis, cornification, excitotoxicity, Wallerian degeneration, ferroptosis

Amyloids

are mutant proteins that form aggregates that are proteases resistant. Brain is particularly sensitive to this

What disease or syndrome is correctly matched with its characteristic? a. Gaucher: deletion of the p arm of chromosome 15 b. Hurlers syndrome: deficiency of alpha iduronidase c. Tay Sachs: deficiency of arylsulfatase A d. Metachromatic leukodystrophy: beta glucosidase deficiency

b. Hurlers syndrome: deficiency of alpha iduronidase

Microtubule transformation growth occurs at ________ end of the tubule

beta

Define Translocations formation and an example using a disorder:

breakage of two chromosome with transfer of one broken segment to another chromosome. Results in altered expression of genes in these translocated regions. (chronic myelogenous leukemia and down syndrome)

Define deletions and an example using a disorder:

breakage or loss of a portion of a chromosome that leads to the loss of specific genes in the deleted region. (cri-du-chat)

Define Isochrome formation and an example using a disorder:

breaking of chromosome at centromere, with one arm of a chromosome being duplicated resulting in a chromosome with two p's or q's. (angelman & down syndrome)

The process of growth of an actin cytoskeletal structure is known as __________. New subunits are added onto the ____________ end. Accessory proteins that allow for branching are called __________. a. nucleation, minus, keratin b. rescue, minus, myosin c. nucleation, plus, Arp2/3 d. replication, plus, dynein

c. Nucleation, plus, Arp 2/3

How does telomerase add the repeated TTAGGG sequence? a. it degrades RNA and then makes dsDNA b. it synthesizes RNA on the ends of DNA c. it uses an integrated RNA template d. it attracts mRNA to the active site

c. it uses an integrated RNA template

Start (restriction point in late G1) transition

cell commits to cell-cycle entry and chromosome duplication What transition?

Necrosis

cell death in response to acute issue

autophagy

cellular self-digestion of old, worn-out organelles and macromolecules

The _______________ allows one copy of each duplicate to be pulled into each daughter cell. A little protein called a ____________ is formed at the centromere and attaches both chromosomes to the ________________.

centromere, kinetochore, mitotic spindle

Microtubules are attached to a microtubule organizing center called the__________. Inside that structure are two___________.

centrosomes; centrioles

Interpret 3p14.3

chromosome 3 on the p arm at location 14.3

___________ and __________ are made from microtubules and motor proteins

cilia and flagella

Major groove is the one that has _____- sequences that regulatory proteins attach to PLUS certain other contact points. These proteins contain "__________________" that bind to the major groove based on the protein's amino acid side chains

cis structural motifs

What does CRISPR stand for?

clustered regularly interspaced short palindromic repeats

•Contact-mediated attraction/repulsion:

contact with an adhesion protein in the substrate

Apoptosis

controlled cellular suicide that occurs mostly in animal cells

For Gaucher disease, what mutations, physical symptoms, where does it commonly appear, and what type of treatment is used?

deficiency of beta- glucosidase Liver and spleen enlargement and glycosphingolipids accumulate Cells appear in bone marrow enzyme replacement therapy

Which of the following events occurs in mitotic prometaphase? a. nuclear envelope reassembly b. formation of the contractile ring c. separation of the sister chromatids d. breakdown of nuclear membrane

d. breakdown of nuclear membrane

Where in the nucleus are you more likely to find transcriptionally inactive chromatin? And what is this called? a. in the center of the nucleus, euchromatin b. in the center of the nucleus, heterochromatin c. on the edge of the nucleus, euchromatin d. on the edge of the nucleus, heterochromatin

d. on the edge of the nucleus, heterochromatin

DISC

death-inducing signaling complex or DISC is a multi- protein complex formed by members of the "death receptor" family of apoptosis -inducing cellular receptors. A typical example is FasR, which forms the DISC upon trimerization as a result of its ligand ( FasL) binding. The DISC is composed of the death receptor, FADD, and caspase 8

G2/M transition

early mitotic events with chromosome alignment on the spindle occur; DNA repair too What transition?

What are the 3 types of interactions between the polypeptide chains?

electrostatic attractions, hydrogen bonds, van der waals attractions

telomerase

enzyme that elongates telomere sequences in DNA, which occur at the ends of eukaryotic chromosomes.

An ________ is a protein that bind one or more ____________, called substrates, and convert them into products

enzyme, ligands

What are conserved regions of DNA or RNA, what percentage of human genome is conserved across species? How much of that percentage codes for proteins?

exons, 5%, 1/3

Extrinsic signaling pathways

extracellular proteins bind to death receptors on a cell surface; have ligand-binding region, one transmembrane domain, and a death domain; belong to TNF (Tumor Necrosis Factor) family.

survival factor

extracellular signals form other cells to avoid apoptosis. Cells w/ no signals cannot import nutrients and eat themselves (autophagy) but eventually starve to death (not apoptosis)

What is an example of a beta sheet? **hint a protein component of silk

fibroin

What is the tertiary structure of a protein?

folding into 3D shape; attractions between different secondary structures

Order of events and mechanisms are secondary to the fact that a ____________________ protein must be bound to DNA (either __________ or ___________) at the ______-regulatory sequence to influence transcription of a target gene

gene regulatory protein directly or indirectly cis- regulatory

What are some examples of effector proteins?

gene regulatory proteins, enzymes, ion channel proteinss, parts of a metabolic pathway, or cytoskeletal proteins

tumor suppressor

gene that appears to help prevent formation of a cancer. Loss- of -function mutations in such genes favor the development of cancer.

Which is found almost exclusively on the extracellular layer (or non-cytosolic side) of the cell membrane?

glycolipid

Angiogenesis

growth of new blood vessels by sprouting from existing ones.

epigenetic inheritance:

heritable changes in phenotype or gene expression caused by mechanisms other than changes in DNA sequence

What happens during deamination reaction?

hydrolysis bumps off NH2 from the cytosine and is replaced with an oxygen to form a uracil and a hydrogen it bonded to the nitrogen

Endosome:

immature lysosome created from Golgi or plasma membrane

intracellular signaling proteins process signals, then ________________ target changes in cell behavior

intracellular signaling proteins process signals, then effector proteins target changes in cell behavior

Activators can act at different steps during the ______________________to promote it ◦______________________ to continue transcription by loading elongation factors ◦_____________________ from promoter to start transcription ◦______________________ to sequence

initiation of transcription Binding to RNA pol Releasing RNA pol Bring RNA pol

____________________ found in vertebrate cells that are required to deal with mechanical stress

intermediate filament

Intrinsic signaling pathways

internal response to injury or hypoxia that is dependent upon release of cytochrome c and other proteins from mitochondria which in turn activate a caspase cascade

What are not conserved regions of the DNA or RNA, and are spliced out during transcription or replication?

introns

Define prion

is an infectious agent that is comprised entirely of a malfolded protein

The infectious ___________ of PrP, known as PrP*, is able to convert normal PrP proteins into the infectious form by changing their ______________. List 3 diseases that involve PrP.

isoform conformation •Mad cow disease •Creutzfeld-Jacob disease •Scrapie

What motor proteins are important in mitotic spindle formation?

kinesins and dyein

Substance bound by a protein is a ___________.

ligand

Define the major and minor grooves of the double helix.

major- wider distance between the back bone structures minor-shorter distance between the back bone structures

What is the purpose of Upf proteins and where do they attach?

marks where there is abnormal splicing and attaches to the EJC (Exon Junction complex) this marks the mRNA for degradation.

Neoplasm

mass of cells or tumor; if benign, then there is no invasion

The ____________ connects all of the proteins such as regulators coactivators, transcription factors, and polymerases together (needed to bring all of the other elements of gene expression together!!)

mediator

Actin filaments are also known as __________, are the helical polymers of the protein _____________.

microfilaments actin

Axoneme made of ________________ and associated proteins in a special pattern

microtubules

Think about the positive and negative ends of the organelle involved in mitotic spindle formation: ____________ end of tubule is in the _______________, ___________ end extends away

minus end of tubule is in the centrosome, plus end extends away

cytochrome c

mitochondrial electron transporter that binds to adapter protein Apaf1 which becomes an apoptosome which activates procaspases

What is a missense mutation?

mutation that changes nucleotides to were codon now codes for diff amino acid

myofibrils in striated skeletal muscle cytoplasm consist of ___________; ________ and __________ (a motor protein) interact there

myofibrils in striated skeletal muscle cytoplasm consist of sarcomeres; actin and myosin (a motor protein) interact there.

Malignant

neoplasms invade nearby tissues. Of tumors and tumor cells: invasive and/or able to undergo metastasis. A malignant tumor is a cancer.

PrP is a normal protein found on the membranes of cells , especially _________; it has 209 amino acids and a mainly ____________ structure

neurons alpha-helical

proto-oncogene

normal gene, usually concerned with the regulation of cell proliferation, that can be converted into a cancer: promoting oncogene by mutation.

List at least 5 universal features of all cells

o Hereditary information storage (DNA) o Cells replicate through templates polymerization o Cells use RNA as an intermediate via transcription o Cells use proteins as enzyme catalyst & the catalytic reactions form new DNA o All cells use tRNA to translate RNA into proteins o Proteins are encoded by specific genes o Free energy is required for many cell processes (ATP is a carrier) o Cells have plasma membranes o Cells can exist with about 300 genes

What is Metachromatic leukodystrophy (MLD) and what treatment is used?

o Metachromatic leukodystrophy (MLD) - Genetic mutation leads to deficiency of arylsulfatase A, allowing buildup of glycosphingolipid in white matter of brain and cord. o Treatment: is supportive or bone marrow transplant.

Angelman syndrome

occurs when paternal gene is imprinted and maternal gene in region UBE3A is deleted that encodes E3 ubiquitin ligase which is imprinted only in brain

Prader-Willi

occurs when the maternal copy of on a gene is imprinted and paternal gene is DELETED that includes small nuclear ribonucleoprotein polypeptide N gene

What is the quaternary structure of a protein?

other peptide chains interact with main protein chain

DNA polymerase requires the energy of the _____________________________ formation that occurs only in the 5' to 3' direction to drive ____________.

phosphodiester bond formation, DNA repair

During elongation, which end are the actin subunits added?

plus end

The ____________ of the side chains of the specific amino acids causes the polypeptide to _________. The _________ side chains gather on the outside, while the _________ chains pack themselves inside as a core. The folded conformation is the ____________ structure of proteins.

polarity, fold polar, nonpolar secondary

What energy can be store in cell membranes in the form of electrochemical gradients?

potential energy

The ______________ structure involves the amino acid sequence. A protein obviously does not look this tidy. Because of the forces between the _________________ of the amino acids, proteins fold into a ______________ structure.

primary side chains secondary

Which structures combined form the tertiary structure?

primary and secondary

Caspase

proteases w/ a cysteine at their active site and that cleave target substrates at specific aspartic acid (D)

Thinking of the protein SRC, which is a _____________________ that adds a phosphate group to other proteins using ________ as the substrate in the cell signaling. There are _______ domains, ______ are regulatory and ______ are responsible for catalytic work.

protein kinase ATP three, two, one

Not all proteins have this ___________ structure; an example is _________, in which several different interconnected proteins (________ chains in this case) join together to form one protein.

quaternary hemoglobin, globin

death receptor

receptor when bound to activates caspases.

-transcription regulatory protein:

recognize and bind to specific DNA sequences near a gene (upstream of the transcription initiation start point which are recognized by transcription regulatory proteins) on a complete strand that either up regulates or down regulates transcription.

sER membranes contain ___________________ enzymes for ____________ function

sER membranes contain cytochrome enzymes for detox function

What is the primary structure of a protein?

sequence of amino acids

DNA repair

set of processes that immediately correct spontaneous changes in DNA

-RNA interference:

short stranded RNA's of 20-30 nucs that guide or interact w other RNAs in the cell and can inhibit translation or catalyze destruction of mRNA. Include miRNA (argonautes, RISC) siRNA (RITS, self-replicating, finds viral or transposable element RNA), and piwiRNA (stops transposons in germ line)

Metaphase to anaphase transition

sister chromatids separate, anaphase triggered What transition?

Fragile X, myotonic dystrophy, and Huntington's disease are examples of

trinucleotide repeats

Microtubules are long, hollow cylinders made of the protein _____________.

tubulin

primary tumor

tumor at the original site at which a cancer first arose. Secondary tumors develop elsewhere by metastasis.

In filament nucleation, why does the subunit assemble and disassemble so rapidly?

weak non covalent linkages

Cyclin-Dependent Protein Kinases (Cdks)

what does Cdks stand for?

¢Basic cause of cancer: damage to specific ____________ (mutations) that accumulate in somatic cells (_________________) over time until a cell loses a critical number of _____________________________ mechanisms and initiates a _______________. ¢__________________ involved in regulating cell growth and differentiation may occur and can lead to _________________ of growth and ___________________ madness If only one mutation were able to convert healthy cells into _____________________ cells, we would not be ____________ organisms ¢Other causes include ________________________ of specific molecules such as ____________ OR chromosome issues ¢Specific genetic alterations are associated with specific _________________.

¢Basic cause of cancer: damage to specific genes (mutations) that accumulate in somatic cells (somatic mutations) over time until a cell loses a critical number of growth-controlled mechanisms and initiates a tumor ¢Mutations involved in regulating cell growth and differentiation may occur and can lead to deregulation of growth and cell cycle madness If only one mutation were able to convert healthy cells into cancerous cells, we would not be viable organisms ¢Other causes include genetic alterations of specific molecules such as integrins OR chromosome issues ¢Specific genetic alterations are associated with specific cancers

List the cell constraints. (there are 8)

¢Signals >>Growth/death factors ¢Genetic or chromosomal issues ¢Cell-cell interactions ¢Adhesion molecules ¢Differentiation ¢Growth and cell division ¢Migration ¢Cell Death

¢__________ is a cellular stress sensor that reacts to various stresses and produces specific responses that stops damaged cells from ______________ Mice with no __________ protein are normal except that they develop ___________ before 10 months of age

¢p53 is a cellular stress sensor that reacts to various stresses and produces specific responses that stops damaged cells from dividing Mice with no p53 protein are normal except that they develop cancer before 10 months of age

§Activated procaspases become either ___________ caspases or _______________ caspases ▪These cleave specific proteins such as ___________, _______________, cell-cell proteins, and _______________ proteins to either start or stop their ___________.

§Activated procaspases become either initiator caspases or executioner caspases ▪These cleave specific proteins such as lamins, endonucleases, cell-cell proteins, and cytoskeletal proteins to either start or stop their function

List RNA polymerases and their specific functions:

· Pol 1: Transcribes 18S, 5.8S, and 28S rRNA · Pol 2: mRNA synthesis, snoRNA, miRNA, siRNA, lncRNA, and most snRNA · Pol 3: tRNA and 5S RNA, some snRNA, and genes for other small RNAs

State the functions of the nucleolus and list the events that occur there:

· Site of rRNA processing and incorporation of rRNA into ribosome subunits · Telomerase and tRNAs assembled here

____________ is the cyclosome or anaphase promoting complex

•APC/C is the cyclosome or anaphase promoting complex

____________ has a plus and minus end; new subunits are added to "_________" _______ end

•Actin has a plus and minus end; new subunits are added to "barbed" plus end

•Actin subunits assemble head-to-tail to form __________ (__________ and ___________)

•Actin subunits assemble head-to-tail to form F-actin (plus end and minus end)

__________, __________, and accessory proteins work together for muscle contraction

•Actin, myosin, and accessory proteins work together for muscle contraction

Generally explain Base Excision Repair

•BER: DNA glycosylases are specific for altered DNA base 1. Hydrolysis by specific glycosylase 2. AP enzymes (apurinic or apyrimidic endonucleases) chew out sugar backbone here 3. DNA polymerase adds new nucleotide 4. DNA ligase seals nick with new sugar piece

Think about pre replication complex: •__________ and _________ are helicase loading proteins

•Cdc6 and Cdt1 are helicase loading proteins

__________ and cyclin ______ = M-Cdk

•Cdk1 and cyclin M = M-Cdk

Chromosomes move along spindle assembly via ______________ and possible depolymerization of __________________

•Chromosomes move along spindle assembly via motor proteins and possible depolymerization of microtubules

_________ are shorter but beat rhythmically and move fluid over cell surfaces; do not move cells examples of where they would be found in the body.

•Cilia are shorter but beat rhythmically and move fluid over cell surfaces; do not move cells •respiratory tract, gut epithelium, inner ear hair cells

_____________ involved at end of S phase to hold sister chromatids together

•Cohesins involved at end of S phase to hold sister chromatids together

Distinct pairs of _____________ and Cdks regulate progression through different stages of the cell cycle. -Activity of Cdks is regulated by association with _________, activating and inhibitory _________________, and the binding of ________ inhibitors.

•Distinct pairs of cyclins and Cdks regulate progression through different stages of the cell cycle. -Activity of Cdks is regulated by association with cyclins, activating and inhibitory phosphorylations, and the binding of Cdk inhibitors.

•Embryonic development requires extensive cell movement; ________ and _________ are essential

•Embryonic development requires extensive cell movement; actin and tubulin are essential

________________ allow cells to swim through liquid media

•Flagella allow cells to swim through liquid media

Formation _________ and _____ serve as nucleation hubs, binding to a preexisting _________ filament to form a web and acting as a _________ end for monomer addition

•Formation Arp2 and 3 serve as nucleation hubs, binding to a preexisting actin filament to form a web and actingas a plus end for monomer addition

•Growth cones "__________" or "_________" based on environmental cues

•Growth cones "grow" or "shrink" based on environmental cues

•Growth is called _________________.

•Growth is called nucleation

Microtubule transformation: •Growth to shrinkage is a "_____________" and shrinkage to growth is a "__________"

•Growth to shrinkage is a "catastrophe" and shrinkage to growth is a "rescue"

What is the cytoskeleton important for?

•Important in cell shape, cell movement, internal structure, intracellular transport, intercellular communication, organelle and cell anchoring

In ____________, chromosome duplication is followed by two rounds of chromosome _____________; very important: DNA breaks are formed in each sister so they hold on to each other (crossover) called _____________________.

•In meiosis, chromosome duplication is followed by two rounds of chromosome segregation; very important: DNA breaks are formed in each sister so they hold on to each other (crossover) called homologous recombination

•In ______________, homologous chromosomes behave independently of each other (they don't line up together) •In _____________, it is critical that homologs recognize each other and come together for ______________.

•In mitosis, homologous chromosomes behave independently of each other (they don't line up together) •In meiosis, it is critical that homologs recognize each other and come together for meiosis I.

•Intermediate filaments do not contain a ______________ binding site (not ATPases)

•Intermediate filaments do not contain a nucleotide binding site (not ATPases)

____________ and _________________ are examples of intermediate filaments

•Keratins and neurofilaments are examples of intermediate filaments

Think about intermediate filaments: •______________ are most diverse family of intermediate filaments •These anchor to ____________ or ___________________ •Alterations in keratins lead to unusual "______________" diseases

•Keratins are most diverse family of these filaments •These anchor to desmosomes or hemidesmosomes •Alterations in keratins lead to unusual "blistering" diseases

_____________________ are large multilayered proteins built on heterochromatin at the _____________ of a chromosome

•Kinetochores are large multilayered proteins built on heterochromatin at the centromere of a chromosome

•Kinetochores are protein structures that help pull the ____________ apart

•Kinetochores are protein structures that help pull the chromatids apart

M-Cdk ________________ key proteins -induces assembly of ________________ in prophase -ensures ___________________ are attached to opposite poles -triggers chromosome __________________ (reorganization of intertwined sisters) -promotes breakdown of ____________________ -rearranges ___________ cytoskeleton

•M-Cdk phosphorylates key proteins -induces assembly of mitotic spindle in prophase -ensures sister chromatids are attached to opposite poles -triggers chromosome condensation (reorganization of intertwined sisters) -promotes breakdown of nuclear envelope -rearranges actin cytoskeleton

Cilia and flagella are made from ______________ and __________________.

•Made from microtubules and motor proteins

•Meiosis differs from mitosis in that homologous chromosomes ___________________, _____________ occurs, and there are two rounds of ___________ and __________________.

•Meiosis differs from mitosis in that homologous chromosomes come together, crossing-over occurs, and there are two rounds of anaphase and cytokinesis.

•Motor proteins attach to _______________ and "walk" using repeated rounds of ___________________. This is done by _________, which is also an _______________.

•Motor proteins attach to microtubules and "walk" using repeated rounds of ATP hydrolysis •Done by tubulin (also an ATPase)

•Movement of the cilia or flagellum produced by ______________

•Movement of the cilia or flagellum produced by axoneme

•Myosin is a motor protein that with ________ forms the ____________ unit of a muscle cell

•Myosin is a motor protein that with actin forms the sarcomere unit of a muscle cell

_________________ must break down for sister chromatids to attach to spindle

•Nuclear envelope must break down for sister chromatids to attach to spindle

Microtubule Transformation: •______________ (growth) occurs in the MTOC using ___________ tubulin and other proteins that serve as a "_________" for the 13 protofilament structure

•Nucleation occurs in the MTOC using gamma tubulin and other proteins that serve as a "template" for the 13 protofilament structure

Think about pre replication complex: •Pre-RC = _____________ + the____________ sequences on dsDNA + ____________ + and ______________________ -works because of low ____________

•Pre-RC = the ORC + the origin sequences on dsDNA + helicase + and helicase loaders -works because of low S-Cdk

•Role of _____________ in actin dynamics and focal adhesion formation •Myocardial developmental defects associated with impaired intracellular junctions that lead to _____________ and extensive prenatal lethality at embryonic day 11.5 of development •Actin disorganized and _____________ (calcium dependent adhesion protein) missing

•Role of PIP5KIγ in actin dynamics and focal adhesion formation •Myocardial developmental defects associated with impaired intracellular junctions that lead to heart failure and extensive prenatal lethality at embryonic day 11.5 of development Actin disorganized and cadherin (calcium dependent adhesion protein) missing

_________ also stimulates increase in histone protein synthesis for _________________ synthesis

•S-Cdk also stimulates increase in histone protein synthesis for nucleosome synthesis

•Spindle formation occurs in the M phase with the help of ____________ and ____________.

•Spindle formation occurs in the M phase with the help of cohesins and condensins

Think about crossing over: •The homologs are tightly connected and __________ (_________) form. •Crossing over is the basis of __________________________.

•The homologs are tightly connected and chiasma (crosses) form. •Crossing over is the basis of homologous recombination

•The ____________________ is where DNA duplication begins...there are many of these along eukaryotic chromosomes. •The ___________________ allows one copy of each duplicate to be pulled into each daughter cell. A little protein called a _______________ is formed at the centromere and attaches both _______________ to the mitotic spindle. •Telomeres are the most interesting. These repeated sequences (GGTTAGGTTA...) form the ends of a chromosome and protect the chromosome from being eaten by ______________ genes.

•The replication origin is where DNA duplication begins...there are many of these along eukaryotic chromosomes. •The centromere allows one copy of each duplicate to be pulled into each daughter cell. A little protein called a kinetochore is formed at the centromere and attaches both chromosomes to the mitotic spindle. •Telomeres are the most interesting. These repeated sequences (GGTTAGGTTA...) form the ends of a chromosome and protect the chromosome from being eaten by DNA repair genes.

•What happens to the proteins in the lumen of the ER? •Many proteins stay in ER, many go ◦Those that stay have a specific retention signal of 4 amino acids (_________) at _________________ terminus; they must be folded properly to remain in the ER lumen ◦Example: _________ is a chaperone protein that stays in the ER lumen that can hold a protein for degradation ◦Others include ____________ and ___________, other heat shock proteins, protein disulfide ___________________

•What happens to the proteins in the lumen of the ER? •Many proteins stay in ER, many go ◦Those that stay have a specific retention signal of 4 amino acids (KDEL) at carboxy terminus; they must be folded properly to remain in the ER lumen ◦Example: BiP is a chaperone protein that stays in the ER lumen that can hold a protein for degradation ◦Others include calnexin and calreticulin, other heat shock proteins, protein disulfide isomerase