CTO - Lecture 5B Mitosis and Meiosis

What is ubiquitination?

(add ubiquitin and mark for degradation by proteosome) The addition of ubiquitin to a substrate protein is called ubiquitination or less frequently ubiquitylation. Ubiquitination affects proteins in many ways: it can mark them for degradation via the proteasome, alter their cellular location, affect their activity, and promote or prevent protein interactions.

FC: What occurs during cytokinesis

- Contractile Ring composed of actin and myosin cleaves cytoplasm into two daughter cells - Begins in Anaphase and ends after Telophase Signals end of M Phase -All organelles must replicate and be divided between the daughter cells

RT- How is the nuclear envelope broken down during mitosis? -The nuclear envelope splits into two halves that migrate to the poles of the mitosing cell -lysosomal degradation is necessary to dissolve the membrane -ubiqutinization labels the membrane for delivery to proteosomes -phosphorylation of lamins results in fragmentation of the nuclear envelope

-phosphorylation of lamins results in fragmentation of the nuclear envelope

What are the two deviations of the cell cycle?

1) Insufficient parameters (when there isn't an adequate environment for reproduction) - cell enters Go or quiescent phase 2) Some cells are terminally differentiated and can't under normal circumstances be recruited to reproduce. This includes skeletal and most nerve cells.

SB: What process is necessary for cytokinesis?

A contractile ring comprised of actin filaments can interact with myosin (actin-based motility) to pinch off the cell into 2 identical daughter cells.

FC: What is the role of the anaphase promoting complex?

APC [Anaphase Promoting Complex] triggers the separation of sister chromatids by promoting the destruction of cohesins.

All cells that complete G2 are likely to go onto which phase of the cell cycle?

All cells that complete G2 are likely to go on to mitosis.

What is Rb? what activates it and how? What does it do? What will happen to the cell if this protein is mutated?

An example of this is a protein called Rb, for retinoblastoma. This is a nuclear protein that inactivates transcription regulators. Activated G1/S Cdk phosphorylates the RB protein and promotes active transcription. This is one of the main control pathways that blocks DNA synthesis if the cell is not in a favorable environment. If this protein is mutated, the cell will replicate regardless of its environment and cancers will develop.

What occurs during anaphase? Describe the mechanism and components involved in carrying out this stage.

Anaphase begins when the chromatids are separated. There are kinesin motors on each of the polar microtubules that push the spindle poles of the cell apart and, at the same time, the kinetochore microtubules shorten, drawing chromatids toward the poles.

Over the course of a cell cycle, how does the number of cyclins vary? What do they bind to? What occurs after this binding?

As it turns out, there are quite a number of cyclins that increase and decrease over the course of a single cell cycle. Each of these binds to a Cdk, and the activated complex phosphorylates very specific proteins.

What occurs during interphase? What occurs during S phase and G2 phase? What is the Go phase?

As we said before the longest of the phases is interphase, where the cells increase in size, DNA and chromosomes are replicated, the centrosome is duplicated. The S phase is where DNA and centrioles replicate while the G2 phase is associated with buildup of certain things necessary to promote mitosis. Many adult cells have left the cell cycle and these are said to be in the G0 phase. The G0 phase, or 'resting phase' is a period in the cell cycle in which cells exist in an inactive, non-cycling state.

Image - apoptosis of hands in mice

As you can see from the images of this mouse paw, programmed cell death is necessary for normal gross structure, as well.

What occurs during metaphase in meiosis? What special process occurs here leading to recombination?

At metaphase in meiosis, homologous chromosomes are paired. The centromere of each pair is attached to a single spindle pole. It is during this metaphase period where synapsis (sites of fusion) with chiasmata (crossing over) appear between adjacent homologous chromosomes, leading to homologous recombination. The sites of chiasmata and also the presence of cohesins link the pairs until they start migrating toward the poles in the anaphase of meiosis I.

What occurs during telophase? What is the result of dephosphorylation of nuclear lamins and nuclear pore proteins? What is the contractile ring that fully forms at the end of telophase?

At telophase the microtubules depolymerize and the nuclear envelope reforms by dephosphorylation of nuclear lamins. This leads to fusion of vesicles of nuclear membrane. At the same time, the nuclear pore proteins are dephopshorylated, leading to their reassembly. The chromosomes begin to decondense in this phase. A ring of actin filaments form around the waist of the dividing cell, with motor proteins resulting in the "contractile ring" that is fully formed at the end of telophase.

At the end of the portion of the cell cycle that the cyclin is engaged in, what processes disposes the cyclin? What happens to any remaining Cdk?

At the end of the portion of the cell cycle that the cyclin is engaged in, the cyclin is disposed of by ubiquitinization and protein degradation by the proteosomes. At that point, although the Cdk remains, it would be inactive.

SB: What intracellular signaling molecule is key in induction of apoptosis?

Capases. These can be activated by external signals or by intracellular processes such as the release of cytochrome c from the mitochondria.

Which enzymes are involved in the final common pathway of apoptosis? What can activate apoptosis? Damage to what cellular organelle is one of the most powerful activators of cell suicide? (and what does it release in this process, which subsequently activate enzymes that initiate apoptosis)

Cells contain enzymes termed caspases, which are a final common pathway for apoptosis. There are many pathways for activation of these caspases. We previously mentioned that high level of activated p53 protein can activate apoptosis. Damage to mitochondria, with the release of cytochrome C is one of the most powerful activators of cell suicide.

RT- In addition to replication of chromosomes, what else is replicated during the S-phase of the cell cycle? Centriole Nucleolus Golgi Endoplasmic reticulum

Centriole

SB: What are checkpoints and when do they occur?

Checkpoints: Places during which the cell cycle may be interrupted if things are not right. G1: Checks to make sure the environment is suitable for cell division and DNA is undamaged. G2: checks to ensure the cell is big enough and that DNA is replicated. M: Metaphase checkpoint ensures all chromosomes are lined up at the metaphase plate.

SB: What occurs during telophase?

Chromosomes approximate the centrosomes. The nuclear envelope reforms as lamins are dephosphorylated and associated vesicles reform. Cytokinesis (division of the cytoplasm) is complete.

SB: What occurs during prophase?

Chromosomes condense (which have been replicated in S-phase) Centrosomes separate and there is the beginning of the formation of spindle poles.

SB: What occurs during metaphase?

Chromosomes line up at the metaphase plate. Kinetochore MTs are attached to spindle poles (centrosomes) and the polar MTs overlap with those from the other spindle pole.

SB: How is the cell cycle regulated?

Cyclins are important cell cycle regulators. Cyclins interact with CDKs that phosphorylate a large number of proteins that contribute to the progress of the cycle. Cyclins activate different CDKs (M-cyclin for mitosis, S-CDK for DNA synthesis). At the end of its part of the cycle, the cyclin is bound to ubiquitin that will tag it for destruction by the proteosomes.

FC: Why is there a G0 phase? Why not just arrest a cell in G1?

Decrease the chances that it will engage in uncontrolled replication. If something goes wrong in G1 phase - much easier to induce into a state of uncontrolled replication. In G0 phase, cell is not actively replicating, if anything happens in G0 phase/something wrong with checkpoint - unlikely to have uncontrolled replication.

What occurs to centrosomes during the S-phase? How does it occur?

During the S-phase, centrosomes are reproduced. This occurs by separation of the 2 centrioles, each of which then becomes the nidus of origin for a partner centriole.

Which is the shortest and most consistent phase of the cell cycle? Do cells have differences in the cycles?

Each cell has some differences in the amount of the overall cycle although the mitosis phase or M phase is always the shortest and is the most consistent of all of the phases.

What cells in the nervous system die by apoptosis?

For example, in the nervous system, many cells that do not make normal connections ultimately die by this process.

RT- A cell that enters the phase of terminal differentiation (where it will not divide again) does so from which phase of the cell cycle? S G2 M G1

G1

RT- Which phase of the cell cycle is longest? G2 S M G1

G1

SB: What are the components of interphase in the cell cycle?

G1 (cell growth), S (DNA replication), G2 (cell growth and replication of organelles)

Image of chiasmata

Here we can see the chiasmata between homologous chromosomes. Note how the previously identical sister chromatids of each pair are no longer identical.

What will be the result if there is no separation of chromosomes at meiosis I or II? What is it termed as?

If there is no separation at meiosis I or meiosis II, an abnormal number of chromosomal copies will occur. This is termed aneuploidy.

How is the centromere region different in meiosis II (compared to meiosis I)? What is the end result?

In meiosis II, note that the centromere region is attached both spindle poles such that it appears more like mitosis. Cleavage of the kinetochore allows sister chromatids to separate.

What must be broken in order to separate the sister chromatids during anaphase?Which enzyme has to be activated just before anaphase? What does it result in (mechanism)?

In order to separate the sister chromatids, cohesins must be broken. There is an enzyme that is activated by phosphorylation just before anaphase called the anaphase promoting complex, or APC. This results in ubiquitinization and destruction of the inhibitory protein, securin, which results in activation of a proteolytic enzyme that breaks cohesin.

What prevents the cleavage of centromere during anaphase of meiosis I?

In the anaphase of meiosis I, notice that the centromeres do not cleve. There is a special protein incorporated in the centromere during meiosis that prevents the cleavage of the centromere in meiosis I.

What are the phases of the cell cycle?

Interphase -G1 phase -S phase -G2 phase Mitosis (M phase) -cytokinesis

Mitosis takes place in a _________ period of time, regardless of how quickly or slowly the cell is dividing. What is the main factor contributing to the length of time of dividing cells?

It is important to recall that all of the dramatic effects of the mitosis or M phase of the cell cycle have taken place in a very short period of time. This is true regardless of how rapidly or slowly a cell is dividing. The main variable in a rapidly versus slowly dividing cells is the duration of the G1 interphase.

Meiosis II and mitosis are not reduction division like meiosis I because the _________________________________________________; therefore, meiosis II is referred to as _____________ _______________..

Meiosis II and mitosis are not reduction division like meiosis I because the number of chromosomes remains the same; therefore, meiosis II is referred to as equatorial division.

What is the importance of meiosis?

Meiosis is necessary to create a haploid germ cell in order to set the stage for fusion of the egg and a sperm to create a zygote with a normal number of chromosomes (diploid). Meiosis is also important for permitting recombination between chromosomes within each of the germ cells. This promotes genetic diversity.

How many divisions does meiosis require? What occurs during each one? How many cycles of DNA replication are required?

Meiosis requires two divisions, the first one reducing the total number of chromosomes, and the second reducing the number of copies of each chromatid. This is accomplished by having a single cycle of replication of DNA, followed by two cell divisions.

What occurs during metaphase? Where are the centrosomes located? What are astral, polar, and kinetochore microtubules?

Metaphase is the easiest phase to recognize because the chromosomes are aligned along the equatorial plate between the two spindle poles. Remember, the centrosomes are located at the spindle poles. Note that there are several features of the organization of the microtubules. Some radiate toward the periphery of the cell membrane called astral microtubules. Some overlap with microtubules from the opposite spindle pole. These are called polar microtubules. Finally, there are microtubules attach directly to kinetochores at the center of the chromosomes. These are called kinetochore microtubules.

What occurs during late prophase? What is it also known as?

Nuclear membrane breaks down, aka prometaphase

What kinds of signals from the environment can trigger apoptosis? (2)

Of course, signals from the environment can also trigger apoptosis and this can either be due to presence of an unfavorable cell environment or lack of normal growth factors to promote continued cell survival.

SB: What is apoptosis and why is it important?

Programmed cell death. It is not inflammatory and is due to the activation of intracellular mechanisms that cause destruction of the cell from the inside with phagocytosis of the resultant debris. It is important for normal development because it will get rid of unwanted cells without tissue damage.

What phase involves condensation of chromosomes, migration of the duplicated centrosomes to opposite poles of the cell, the assembly of microtubules and some changes in the nucleus that include disappearance of the nucleolus.

Prophase in mitosis (first stage)

SB: What happens during anaphase?

Separation of paired sister chromatids moving toward the simple poles (centrosomes). Dynein on the astral microtubules pull, kinesins on the polar MTs push the chromosomes apart and progressive depolarization of the kinetochore MTs pull the chromosomes apart.

What is the mechanism of S-Cdk with regards to ORC? What is the ORC? What inhibits the ORC?

Some of the mechanisms for cyclins have been well studied and provide a good illustration of general principles. One such example is the S-Cdk that promotes synthesis of DNA in the S phase of the cell cycle. Remember, of course, that S-cyclin consists of a complex between a cyclin and a Cdk molecule. It is also important to know that there are defined places within chromosomes that are the beginning sites for replication. These have a specific nucleotide sequence called an "origin of replication" sequence. There is a complex of proteins called the origin recognition complex, or ORC, that mates with the site on the gene and promotes replication. However, this ORC is inhibited by binding to a pre-replicative complex. The S-Cdk phosphorylates part of this pre-replicative complex and frees the origin recognition complex to begin the process of assembly of the replication fork that will copy that part of the genome.

Which cells are terminally differentiated?

Some of these cells can be coaxed back into the cell cycle later although some cells are terminally differentiated and can't under normal circumstances be recruited to reproduce. This includes skeletal muscle and most nerve cells.

Where are telomeres located? How is transcription of DNA at the end of the strand and what is the role of telomeres in this process? What limits the number of cell cycles? What enzyme contributes to lengthening telemores and immortalization of cells?

Telomeres are located at the end of each chromosome. Transcription of DNA is not efficient towards the end of a DNA strand. With subsequent copies, the ends of the strands of DNA begin to shorten. Since the telomeres do not contain important genetic material, they essentially allow all of the important information to be copied. However, with each successive cell cycle of replication, they shorten. Once they've reached a certain length, subsequent copies would have a high risk of not transcribing important information. Normal cells stop replicating when their telomeres shorten beyond a certain degree. This limits the number of cell cycles. An enzyme called telomerase can result in lengthening of telomeres and contribute to immortalization of cells.

When can the cell cycle be interrupted and why? Can cells return to the cell cycle after interruption?

The cell cycle can be interrupted in interphase. This can occur when there isn't an environment that's adequate for reproduction. Some of these cells can be coaxed back into the cell cycle later although some cells are terminally differentiated and can't under normal circumstances be recruited to reproduce. This includes skeletal muscle and most nerve cells.

What is the centromere made up of (2 things)? How many different proteins make it up?

The centromere is a complex structure, which includes both the chromatin in the area and the kinetochore proteins. There are more than 60 different proteins that go into forming this vital structure

During prometaphase, what attaches the condensing chromosomes to microtubules? What process does this begin?

The condensing chromosomes attach to microtubules by their kinetochore. This begins the process of alignment of chromosomes.

The events that occur in ___________ but not ___________include homologous chromosomes pairing up, crossing over, and lining up along the metaphase plate in tetrads.

The events that occur in meiosis but not mitosis include homologous chromosomes pairing up, crossing over, and lining up along the metaphase plate in tetrads.

Image - centromere

The figure in the upper right shows the location of the centromeres of these chromosomes fluorescing green.

What is the first stage of mitosis? What occurs during this stage (4)?

The first stage of mitosis is prophase. Prophase is accompanied by condensation of chromosomes, migration of the duplicated centrosomes to opposite poles of the cell, the assembly of microtubules and some changes in the nucleus that include disappearance of the nucleolus.

In order to phosphorylate other proteins, Cdk must be bound to _______ and also must be _________________ at an activating site but not at an inhibiting site.

The fundamental principle is that there are enzymes called cyclin-dependent kinases or Cdks that are present in the cell. These Cdks are inactive by themselves. However, when bound to specific cyclins they gain enzymatic activity, which can be further regulated by phosphorylation at a couple of sites. So, in the example shown, Cdk must be bound to the cyclin and also must be phosphorylated at an activating site but not at an inhibiting site. As you can imagine, this can result in sudden change in function of the complex by addition or subtraction of a phosphate molecule. In turn, activated cyclin-dependent kinases' main function is to phosphorylate other proteins within the cell. These phosphorylated proteins can then have profound effects on the cell cycle.

What is the role of cyclin-dependent kinases (Cdks) in cell regulation/cylce?

The fundamental principle is that there are enzymes called cyclin-dependent kinases or Cdks that are present in the cell. These Cdks are inactive by themselves. However, when bound to specific cyclins they gain enzymatic activity, which can be further regulated by phosphorylation at a couple of sites. So, in the example shown, Cdk must be bound to the cyclin and also must be phosphorylated at an activating site but not at an inhibiting site. As you can imagine, this can result in sudden change in function of the complex by addition or subtraction of a phosphate molecule. In turn, activated cyclin-dependent kinases' main function is to phosphorylate other proteins within the cell. These phosphorylated proteins can then have profound effects on the cell cycle.

What enzymatic functions do mechanisms of regulation of the cell cycle involve? What enzymes are required?

The mechanisms of regulation of the cell cycle are extremely important and quite complex. The field has exploded since the early 80s when Timothy Hunt identified the first cyclin while studying replicating sea urchin cells. Since that time, our understanding has advanced dramatically but so has our recognition of the complexity inherent in this control system. Remarkably, the system is virtually identical across species from yeast to humans. Not surprisingly, this is one of the fundamental areas of study in cancer research given that uncontrolled replication is one of the hallmarks of cancers. The process relies on phosphorylation and dephosphorylation of proteins, which dramatically changes their functional state. This process requires enzymes called kinases and phosphatases.

What does pro-metaphase involve? When does it occur during mitosis? What attaches the condensing chromosomes to microtubules? What process does this begin?

The next phase, that is, pro-metaphase, includes the dissolution of the nuclear envelope into vesicles that are now scattered in the cell. It occurs after prophase.

What is the name of the product of the B-cell lymphoma gene that is anti-apoptotic? What would occur in the case of unregulated transcription of this gene?

The product of the B cell lymphoma 2 gene, also called Bcl 2, is anti-apoptotic. Therefore, unregulated transcription of this gene, with high levels of the Bcl 2 protein, may protect cancer cells from signals that would normally produce cell suicide. This is yet another mechanism whereby gene mutations can promote cancer.

What pulls chromosomes towards centrosome? What occurs during anaphase A? What occurs in anaphase B? What is the net result?

There are several factors that go into movement of chromatids. The chromosomes themselves are pulled towards the centrosome mainly by shortening of the kinetochore microtubules. Motor proteins pull the kinetochore along the shortening tubule. That process is considered anaphase A. Simultaneously, the centrosomes are pushed apart by kinesin motors that move the polar microtubules in relationship to one another. This is called anaphase B. the net result is movement of chromatids toward the poles.

What is the role of the G1 checkpoint? S-phase checkpoint? G2 checkpoint? and M-phase checkpoint? How do these checkpoints work (in relation to Cdks)? What would be the result of abnormalities in checkpoint proteins?

There are several well-established examples checkpoints. For example, there is a G1 checkpoint that surveys for a favorable environment and the presence of appropriate growth factors and external signals. There is an S-phase checkpoint, controlling the entry of the cell to the synthesis phase of DNA, that checks for damaged DNA. There is a G2 checkpoint, which checks that all of the DNA has been replicated whether there is damaged DNA. And there is an M-phase checkpoint that controls for all chromosomes being properly aligned on the mitotic spindle. Many of these checkpoints work by phosphorylation or dephosphorylation of regulatory sites on Cdks. Abnormalities of these checkpoint proteins will result in cancers.

SB: What occurs during prometaphase?

There is a breakdown of the nuclear envelope with phosphorlyation of nuclear lamins. Spindle fibers (MTs) attach to the kinetochores of chromosomes (kinetochore MTs)

Image - distribution of chromosomal material at various stages of cell cycle

This a very nice illustration of the distribution of chromosomal material in the nucleus at various stages from interphase in the upper left through metaphase in the lower left and then on to segregation of daughter chromatids with cytokinesis in the lower right.

What are the roles of S-Cdk and M-Cdk? How are the cyclin/cdk complexes turned on and off?

This cartoon shows a very simplified version of two of the earliest- known cyclin/Cdk complexes. These were called S-Cdk, because it promotes the S phase of the cell cycle, and M-Cdk because it promotes entry of the cell into mitosis. While the Cdk molecules are present constantly, notice that the S cyclin and M-cyclin are present for much shorter periods. They do, indeed, cycle during the cell cycle. Remember, the cyclin/Cdk complex also can be turned on and off by phosphorylation at the activating and inhibiting sites, respectively.

Image of cytokinesis (what is cytokinesis)?

This cartoon shows cytokinesis with the contractile ring pinching the cytoplasm into 2 daughter cells. Note that each of the daughter cells is beginning to assume the structure of a normal interphase cell.

Image - Condensins fold and pack chromosomes

This cartoon shows the engagement of condensins in the folding and packing of chromosomes.

What are the three types of microtubules involved in mitosis?

This cartoon shows the three types of microtubules.... The astral microtubules, the polar microtubules... and the kinetochore microtubules attached to the kinetochores of the condensed chromosomes.

What is the nuclear envelope and what occurs to it during prometaphase? What is the mechanism by which the nuclear envelope disintegrates? Which type of cytoskeletal component is involved in this process?

This cartoon shows what happens to the nuclear envelope in prometaphase. As you may recall, the nuclear envelope is a structure with 2 layers of membrane surrounding the space. This is supported by the nuclear lamina that's created from an intermediate filament called lamin. Phosphorylation of lamin and of nuclear pore proteins cause them to disassociate. In that process the lamins remain connected to the adjacent nuclear envelope membrane and cause the fragments of the nuclear envelope to form vesicles. This allows for rapid disassembly of the highly complex nuclear envelope and also sets the stage for these lamins and vesicles to fuse at the end of mitosis, restoring the structure of the nucleus. This is how the disassembly and assembly of the nucleus can take place so quickly.

Image of centrosome - where is the plus end of microtubules?

This cartoon version shows the same thing, depicting the gamma tubulin surrounding the centriole. Notice that the plus end of microtubules is away from the centrosome.

Image - electron micrograph of centromere pulled apart

This electron micrograph shows microtubules attached to the centromere of a chromatid that is being pulled apart from its sister.

Image - tug of war chromosmal alignment

This electron micrograph shows the organization of the centrosomes, microtubules and chromosomes very clearly. You can imagine the tug of war going on to produce the physical alignment of chromosomes.

Image of kinetochore in centromere with microtubules attaching them

This figure shows the condensed chromosome with a kinetochore located in the centromere region of the chromosome. Note the kinetochore microtubules attaching to it.

Pro-metaphase occurs due to phosphorylation of the __________ due to very special kinases that are activated by __________.

This is happening due to phosphorylation of the lamins due to very special kinases that are activated by cyclins.

What is a centrosome? What does it consist of?

This photomicrographs shows a centrosome, which is the microtubule organizing center. Remember, the centrosome consists of centriole with surrounding gamma tubulin rings that form the base of the microtubules.

Image - apoptosis in digestive tract, why do we need apoptosis here?

This process continues through adulthood where old cells in rapidly replicating regions, such as this gut epithelium, must be cleared away to make room for the new cells.

What is apoptosis? What is it essential for?

This process has been termed apoptosis. This is a non-inflammatory programmed cell death that's essential to normal development and to destruction of damaged or deranged cells.

Alignment of chromosomes during metaphase occurs by a tug-of-war between ________________________ attached to opposite chromatids at the ______________.

This process of alignment of the chromosomes occurs by a tug-of-war between kinetochore microtubules attached to opposite chromatids at the kinetochore.

In which phase of the cell cycle does the cell spend the majority of its time? What occurs during the G1, S, and G2 phase? What are the phases of mitosis?

This schematic shows a representation of cell cycle in a culture of bone cells. Note that it takes approximately 38 hours for the cells to reproduce. The cell spends the majority of this time in interphase which includes a G1 phase an S-phase and a G2 phase. The S- or synthesis phase is where chromosomes and centrosomes are duplicated while the G1 phase is an initial growth phase and the G2 phase begins the growth and duplication of some essential organelles. Also note that mitosis itself takes a relatively short amount of time. This represents only an hour or so of the entire cycle. Mitosis itself is broken into phases that include the prophase metaphase anaphase and telophase.

Which two proteins in the nucleus are important for the high degree of organization of DNA? What are their roles?

Two proteins within the nucleus are important for the high degree of organization of DNA. These include condensins that increase coiling of DNA within the chromosome and cohesins that bind sister chromatids together.

What is the purpose of the cell cycle? What must the daughter cells contain?

Ultimately, the functions of the cell cycle are to copy the genetic material and pass it on to the next generation of cells, along with the machinery to make identical replica cells. Replicated chromosomes must be segregated into the daughter cells so that the entire genome is represented. Additionally, all the other cell constituents must be duplicated within the daughter cells.

When the homologous chromosomes separate and move to opposite poles during meiosis I, the ploidy level is reduced from two to one, which is referred to as a _______________________ ________________.

When the homologous chromosomes separate and move to opposite poles during meiosis I, the ploidy level is reduced from two to one, which is referred to as a reduction division.

each different cyclin/Cdk complex targets specific proteins within the cell that regulate many functions that must happen at specific times during the cell cycle. What are some examples of these target proteins? What effects do they have on downstream Cdk functions?

While the details of this slide are not important for you to memorize, notice that each different cyclin/Cdk complex targets specific proteins within the cell that regulate many functions that must happen at specific times during the cell cycle. Some of these target proteins are transcription factors that will result in transcription of specific genes, some have the role of phosphorylating other kinases or phosphatases, and some directly affect downstream Cdk functions. Therefore, one phase of the cell cycle may push the next phase along or play a role in ending the prior phase

What parts of cell cycle ensure that it proceed normally without errors and serve as quality control stages? How do these work?

While this cell cycle is very important to the replication of a cell, it's also important that it proceed normally and without errors. Therefore, there are quality control stages that are called checkpoints. Some of these checkpoints are very well understood, while new checkpoint mechanisms are still being discovered. These checkpoints typically work by controlling the activity of the cyclin/Cdk complexes in one way or another.

In what gene do the majority of cancer cells (regardless of the particular type of tumor) have abnormalities? What activates the product of this gene and what does it do? What are the 2 categories of kinases that can activate this protein and what will be the effects?

Yet another highly clinically important regulator is the p53 gene. The majority of cancer cells, regardless of the particular type of tumor, have abnormalities of this protein. The p53 protein is being constantly produced by the cell. It's also being constantly broken down so there is very little in the cell. The p53 protein is activated by phosphorylation, which stabilizes the protein and prevents breakdown. There are a large number of kinases that can activate the p53 protein, and these kinases fall into 2 basic categories: those that increase activity with cell stress and those that increase activity in the presence of damaged DNA. Therefore, a highly stressed cell, or one with broken DNA will have high levels of activated p53, which will prevent replication. This is good because, in both of these situations, it would be ill advised for the cell to reproduce. Fortunately, this activated P 53 binds to regulatory regions of a gene producing a protein that then inhibits the cyclin/Cdk complexes that promote the S phase of the cell cycle. This allows time for the cell to repair. If it is unable to do so, the activated p53 gene can also activate mechanisms for apoptosis or cell suicide.

What is the kinetochore?

a complex of proteins associated with the centromere of a chromosome during cell division, to which the microtubules of the spindle attach.

What is a proteosome?

break peptide bonds; Proteasomes are protein complexes inside all eukaryotes and archaea, and in some bacteria. In eukaryotes, proteasomes are located in the nucleus and the cytoplasm. The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds.

FC: Which is not a feature of telophase? dephosphorylation of lamin degradation of M-cyclin completion of contractile ring dispersion of chromatin

contractile ring (actin) is only starting to form in telophase; only completed during cytokinesis

Activated P 53 binds to regulatory regions of a gene producing a protein that then inhibits the ____________________ that promote the S phase of the cell cycle. This allows time for the cell to repair. If it is unable to do so, the activated p53 gene can also activate mechanisms for ________________.

cyclin/Cdk; apoptosis

The daughter cells produced by mitosis are identical, whereas the daughter cells produced by meiosis are ____________________________________________________________________________.

different because crossing over has occurred.

Generally, in mitosis, diploid cells are partitioned into two new diploid cells, while in meiosis, _________________________________________________________________________________.

diploid cells are partitioned into four new haploid cells.

FC: During anaphase, kinetochore microtubules....

disassemble; as MT falls apart, dynein motor proteins will pull kinetochore and walk it back towards MTOC (centrosome) and prevent disassembly from making Kinetochore MT's from losing grip on chromosomes

RT- Which of the following most closely correlates with the transition from metaphase to anaphase? enzymatic degradation of cohesin formation of a contractile ring dispersion of the nucleolus attachment of chromosomes to kinetochore microtubules phosphorylation of nuclear lamins

enzymatic degradation of cohesin

FC: If somatic cells have 2n chromosomes (46) and x amount of DNA, what would a cell at the end of meiosis I have? n; ½x n; x 2n; ½x 2n; x ½n; ½x ½n; x

n; x (but why?)

SB: What is the role of p53?

p53 is phosphorlyated in the presence of damaged DNA. It turns on the gene for p21 which produces a protein that will arrest the cell cycle until the DNA is repaired.

RT- The nuclear membrane disassembles in which phase of mitosis? prometaphase prophase anaphase metaphase telophase

prometaphase

What is the centromere?

region of DNA where sister chromatids attach

In mitosis, the daughter cells have the same number of chromosomes as the parent cell, while in meiosis ___________________________________________________________________________.

the daughter cells have half the number of chromosomes as the parent.