Chapter 18

Cell-Cycle Control is Similar in All Eukaryotes

4 phases gap phases allow time to proliferate and enter S phase

The Activity of Cyclin-Cdk Complexes Depends on

Phosphorylation and Dephosphorylation For M-Cdk to be active, inhibitory phosphates must be removed mitotic Cdk+inhibitory kinase (Wee1)--> phsophorylates M-cdk to keep it inactive inactive M-Cdk+activating phosphatase (Cdc25)-->active M-Cdk

cytokinesis

The Mitotic Spindle Determines the Plane of Cytoplasmic Cleavage --The cleavage furrow is formed by the action of the contractile ring underneath the plasma membrane The Contractile Ring of Animal Cells Is Made of Actin and Myosin Filaments --The contractile ring divides the cell in two --Animal cells change shape during M phase --fibroblasts round up in M phase Cytokinesis in Plant Cells Involves the Formation of a New Cell Wall --cell wall forms from golgi derived vesicles --Cytokinesis in a plant cell is guided by a specialized microtubule-based structure called the phragmoplast (ensure golgi materials to the right spot) Membrane-Enclosed Organelles Must Be Distributed to Daughter Cells When a Cell Divides

Cdk Activity Can be Blocked by Cdk Inhibitor Proteins

The activity of a Cdk can be blocked by the binding of a Cdk inhibitor p27 binds to the active cyclin-cdk complex and inactivates it....produces a trimeric complex

Cyclin Concentrations are Regulated by Transcription and by Proteolysis

The activity of some Cdks is regulated by cyclin degradation ubiquitylation of cyclin by APC (anaphase promoting complex...its a ubiquitin ligase) results in destruction of cyclin in proteasome which inactivates Cdk apc adds four ubiquitous the cyclin

Summarize G1 phase

The cell-cycle control system can halt the cycle at specific transition points to ensure that intracellular and extracellular conditions are favorable and that each step is completed before the next is started. Some of these control mechanisms rely on Cdk inhibitors that block the activity of one or more cyclin-Cdk complexes.

summarize cell-cycle control system

The cell-cycle control system coordinates events of the cell cycle by sequentially and cyclically switching on and off the appropriate parts of the cell-cycle machinery. The cell-cycle control system depends on cyclin-dependent protein kinases (Cdks), which are cyclically activated by the binding of cyclin proteins and by phosphorylation and dephosphorylation; when activated, Cdks phosphorylate key proteins in the cell. Different cyclin-Cdk complexes trigger different steps of the cell cycle: M-Cdk drives the cell into mitosis; G1-Cdk drives it through G1; G1/S-Cdk and S-Cdk drive it into S phase. The control system also uses protein complexes, such as APC, to trigger the destruction of specific cell-cycle regulators at particular stages of the cycle.

The Cell-Cycle Control System Can Pause the Cycle in Various Ways

The cell-cycle control system uses various mechanisms to pause the cycle at specific transition points G2-M=inhibition of activating phosphatase (Cdc25) blocks entry to mitosis M=inhibition of APC activation delays exit from mitosis G1=Cdk inhibitors block entry to S phase

A Cell-Cycle Control System

Triggers the Major Processes of the Cell Cycle The cell-cycle control system ensures that key processes in the cycle occur in the proper sequence M phase: Are all chromosomes properly attached to the mitotic spindle? --> pull chromosomes apart G1: Is environment favorable?-->enter S phase G2: Is all DNA replicated? Is all DNA damage repaired?-->enter mitosis

The Eukaryotic Cell Cycle

Usually Includes Four Phases Cells reproduce by duplicating their contents and dividing in two, a process called the cell cycle 1.cell growth and chromosome duplication 2. chromosome segregation 3. cell division more specifically G1, S (DNA replication), G2, and M (mitosis-nuclear divsion, and ctyokinesis-cytoplasmic division.) interphase=G1, S, and G2 G=gap Flow cytometry of a population of proliferating cells --determines around of fluorescence in cells -cells that have 2 nuclei will have more flurorescence than those that have not.

interphase

G1, S, G2 During interphase, the cell increases in size. The DNA of the chromosomes is replicated, and the centrosome is duplicated

M phase

M-Cdk Drives Entry Into M Phase and Mitosis --inactive M-cdk needs to be dephosphorylated (2 P removed) by Cdc25 phosphatase to be activated. M-cdk activates Cdc25 --Activated M-Cdk indirectly activates more M-Cdk, creating a positive feedback loop Cohesins and Condensins Help Configure Duplicated --Cohesins and condensins help to configure duplicated chromosomes for segregation. --form cohesion rings around sister chromatids...At right time APC will clip these rings --condensin rings bring chromatin fibers together. helps condense chromatin. -cohesisn found at centromere Chromosomes for Separation Different Cytoskeletal Assemblies Carry Out Mitosis and Cytokinesis --Two transient cytoskeletal structures mediate M phase in animal cells...mitotic spindle and contractile ring (polymerization of actin which recruits myosin allows it to pinch off) M Phase Occurs in Stages

S phase

S-Cdk Initiates DNA Replication and Blocks Re-Replication The initiation of DNA replication takes place in two steps --ORC binds origin of replication. They are unrecognized when Cdc6 is bound. CdC6 is released and allows DNA helices to bind. Therefore have a pre replication complex. then have an S-cdk which phosphorylates the ORC and activates the helices. This allows for the recruitment of replication machine. Incomplete Replication Can Arrest the Cell Cycle in G2 To summarize: S-Cdk initiates DNA replication during S phase and helps ensure that the genome is copied only once. The cell-cycle control system can delay cell-cycle progression during G1 or S phase to prevent cells from replicating damaged DNA. It can also delay the start of M phase to ensure that DNA replication is complete.

proteolysis

During metaphase, duplicated chromosomes gather halfway between the two spindle poles APC triggers the separation of sister chromatids by promoting the destruction of cohesins

principle stages of M phase in animal cells

1. prophase --At prophase, the duplicated chromosomes, each consisting of two closely associated sister chromatids, condense. Outside the nucleus, the mitotic spindle assembles between the two centrosomes, which have begun to move apart. 2.prometaphase --Prometaphase starts abruptly with the breakdown of the nuclear envelope. Chromosomes can now attach to spindle microtubules via their kinetochores and undergo active movement. 3. metaphase --At metaphase, the chromosomes are aligned at the equator of the spindle, midway between the spindle poles. The kinetochore microtubules on each sister chromatid attach to opposite poles of the spindle. --Chromosomes are most condensed at metaphase 4.anaphase --At anaphase, the sister chromatids synchronously separate and are pulled slowly toward the spindle pole to which they are attached. The kinetochore microtubules get shorter, and the spindle poles also move apart, both contributing to chromosome segregation. 5.telophase --During telophase, the two sets of chromosomes arrive at the poles of the spindle. A new nuclear envelope reassembles around each set, completing the formation of two nuclei and marking the end of mitosis. The division of the cytoplasm begins with the assembly of the contractile ring. all of theses 5 phases are in mitosis (know order) cytokinesis (a part of M phase but not mitosis) --During cytokinesis of an animal cell, the cytoplasm is divided in two by a contractile ring of actin and myosin filaments, which pinches the cell into two daughters, each with one nucleus. KNOW THE PICTURES

control of cell numbers and cell size

Apoptosis Helps Regulate Animal Cell Numbers --Apoptosis in the developing mouse paw sculpts the digits --As a tadpole changes into a frog, the cells in its tail are induced to undergo apoptosis Apoptosis Is Mediated by an Intracellular Proteolytic Cascade --Cells undergoing apoptosis die quickly and cleanly -two inactive procaspase have prodomains cleaved leads to one active caspase -one initator caspace activates executioner caspases --caspace y-->cleave of nuclear lamin --caspace z--cleavage of a cytosolic protein The Intrinsic Apoptotic Death Program Is Regulated by the Bcl2 Family of Intracellular Proteins --apoptotic stimulus is received but he mitochondria. leads to activation of Box or Bak molecules which leads to the release of cytochrome C from the mitochondria.cytochrome C binds to an anadaptor protein and activates it leading to the assembly of a 7-headed complex which is involved in the recruitment of procaspace 9 which forms an apoptosomes which forms the space cascaded leading to apoptosis --Bax and Bak are death-promoting members of the Bcl2 family of intracellular proteins that can trigger apoptosis by releasing cytochrome c from mitochondria Extracellular Signals Can Also Induce Apoptosis --Activated death receptors initiate an intracellular signaling pathway that leads to apoptosis --killer lymphocyte has Fas ligand. cell to cell contact with Fas ligand and fas death receptor leads to assebly of DISA which leads to activation of caspase-8 which activates exectutioner caspaces and triggers apoptosis Animal Cells Require Extracellular Signals to Survive, Grow, and Divide Survival Factors Suppress Apoptosis --Cell death can help adjust the number of developing nerve cells to the number of target cells they contact --Survival factors often suppress apoptosis by regulating Bcl2 family members...suvival factor bind to and activated receptor which activates transcription regulator. which activates Bcl 2 gene and the Bcl2 proteins ins formed and blocks apoptosis Mitogens Stimulate Cell Division by Promoting Entry into S Phase Growth Factors Stimulate Cells to Grow --Extracellular growth factors increase the synthesis and decrease the degradation of macromolecules --The cells in an animal can differ greatly in size Some Extracellular Signal Proteins Inhibit Cell Survival, Division, or Growth --Mutation of the myostatin (keeps muscle cells small) gene leads to a dramatic increase in muscle mass

G1 phase

Cdks are Stably Inactivated in G1 (triggers them to enter in G0) --The transition from G1 to S phase offers the cell a crossroad. The cell can either proceed to S phase, pause, withdraw to G0 (where cells just hang out), withdraw permenently and terminally to differentiate. Mitogens Promote the Production of the Cyclins that Stimulate Cell Division --One way in which mitogens stimulate cell proliferation is by inhibiting the Rb protein --mitogen binds to a receptor (usually an RTK) which triggers an intracellular signaling pathway. active Rb binds to and inactivates transcription factors. when Rb is phosphorylated (by G1 and G1/s Cdks) it is deactivated and the transcription regulator and bind to the gene and initiate transcription DNA Damage Can Temporarily Halt Progression Through G1 --DNA damage can arrest the cell cycle in G1 --DNA damage activates protein kinases that phosphorylate p53 thereby activating and stabilizing it. the active p53 binds t and turns on p21 gene which produces p21 (idk inhibitor protein) which binds to and inactivates g1/S-cdk and S-cdk Cells Can Delay Division for Prolonged Periods by Entering Specialized Nondividing States ex by entering G0

mitosis

Centrosomes Duplicate To Help Form the Two Poles of the Mitotic Spindle --Sister chromatids separate at the beginning of anaphase --The centrosome in an interphase cell duplicates to form the two poles of a mitotic spindle --microtubules pointing away are called the asters --microtubules touching (interpolar) are stabilized by contact and by motor proteins -motor proteins at kinetochore --kinetichore microtubule attach to kinetochore The Mitotic Spindle Starts to Assemble in Prophase --A bipolar mitotic spindle is formed by the selective stabilization of interacting microtubules Chromosomes Attach to the Mitotic Spindle at Prometaphase --Three classes of microtubules make up the mitotic spindle-aster microtubules, kinetochore microtubules and interpolate microtubules Chromosomes Assist in the Assembly of the Mitotic Spindle --Motor proteins and chromosomes can direct the assembly of a functional bipolar spindle in the absence of centrosomes Chromosomes Line Up at the Spindle Equator at Metaphase --During metaphase, duplicated chromosomes gather halfway between the two spindle poles Proteolysis Triggers Sister-Chromatid Separation at Anaphase --APC triggers the separation of sister chromatids by promoting the destruction of cohesins....APC ubiquinates the inhibitory proteins (securing) which is attached to the inactive proteolytic enzyme (separase) which activates separate. seperase cleaves cohesins allowing the sister chromatids to separate Chromosomes Segregate During Anaphase --Two processes segregate daughter chromosomes at anaphase. ---anaphase A chromosomes are pulled poleward. kinetochore has proteins that depolymerize microtubule, shortening it, without letting go of the chromosome. ---anaphase B poles are pushed and pulled apart...sliding force generated by interpolar microtubules from opposite poles to push the poles apart. a pulling force by aster microtubules acts to pull the poles toward the cell cortex thereby moving the poles apart --usually multiple microtubules attached at kinetochore. An Unattached Chromosome Will Prevent Sister-Chromatid Separation --checkpoint checks for this The Nuclear Envelope Re-forms at Telophase --phosphorylation of nuclear pore proteins and lamins triggers the lamins to form vesicles of the membrane. (at pro metaphase) --dephosphorylation of nuclear pore proteins and lamins allows the nuclear envelope to reassemble(telophase) --contained fusion of nuclear envelope vesicles (interphase)

summarize mitosis

Centrosomes duplicate during S phase and separate during G2. Some of the microtubules that grow out of the duplicated centrosomes interact to form the mitotic spindle. When the nuclear envelope breaks down, the spindle microtubules capture the duplicated chromosomes and pull them in opposite directions, positioning the chromosomes at the equator of the metaphase spindle. The sudden separation of sister chromatids at anaphase allows the chromosomes to be pulled to opposite poles; this movement is driven by the depolymerization of spindle microtubules and by microtubule-associated motor proteins. A nuclear envelope re-forms around the two sets of segregated chromosomes to form two new nuclei, thereby completing mitosis.

Different Cyclin-Cdk Complexes Trigger Different Steps in the Cell Cycle

Distinct Cdks associate with different cyclins to trigger the different events of the cell cycle G1-cdk G1-scdk S-cdk Mcdk

The Cell-Cycle Control System Depends on Cdks

Progression through the cell cycle depends on cyclin-dependent protein kinases (Cdks) -Cdk's (heterodimeric protein kinase) bind cyclin (regulatory subunit) -have a family of Cdks The accumulation of cyclins helps regulate the activity of Cdks -high concentration at mitosis Mcdk-->active in M phase A mature Xenopus egg provides a convenient system for studying the cell cycle --inject cytoplasm from m-phase cell, oocyte is driven into M phase --inject cytoplasm from interphase, nothing happens MPF activity was discovered by injecting Xenopus egg cytoplasm into Xenopus oocytes

Summarize the overview of the cell cycle

The eukaryotic cell cycle consists of several distinct phases. In interphase, the cell grows and the nuclear DNA is replicated; in M phase, the nucleus divides (mitosis) followed by the cytoplasm (cytokinesis). In most cells, interphase consists of an S phase when DNA is duplicated, plus two gap phases—G1 and G2. These gap phases give proliferating cells more time to grow and prepare for S phase and M phase.