Lec 22: Cell Cycle Flashcards
what is one of the main things that defines life?
The ability to self-replicate
Apoptosis:
programmed cell death (that is built into the cell)
ex. an immune cell that proliferates to fight an infection and then goes through apoptosis when it is no longer needed
causes of cancer
cancer is when there is more of a type of a cell than there should be. It can be due to uncontrolled growth, or can be due to lack of appropriate cell death
Four phases of the eukaryotic cell cycle
M phase
G1 phase
S phase
G2 phase
the gap phases are times to get materials together and make sure the conditions are right, pass checkpoints, etc
Cyclins
Cyclin concentrations regulate cell cycles
Kinases put phosphate groups onto other proteins
CDK phosphorylation/dephosphorylation
Two major cyclin-Cdk complexes
2 major classes:
1) active in m-phase
2) active in S-phase (DNA replication)
CDK inhibitor proteins
Serve as brakes on checkpoints
gene dosage:
missing one chromosome means making only half the protein
G0 state
permanently dissassembles the things needed to replicate
G1 checkpoint
No definite answer. It might help mistakes from being made with cells that need to be withdrawn from the replication process, and it might be that the reproductive machinery is metabolically expensive to keep up
S phase
G1- S phase: Every chromosome has at least a few replications of origin, and there are proteins that sit on them. S-cdk phsphorylates the origin replication complex, and initiates the replication process
P53
Mammals do a bad job of fixing double-stranded DNA breaks, and DNA damage can block the progression of the cell cycle.
DNA damage activates p53
Elephants rarely get cancer, although they have about 10 times the cell mass of humans. They have 20 copies of p53
peak 1 is G1, peak 2 is G2/M. the space between G1 and G2 is the S phase
M-phase (mitosis overview)
Prophase
stage 1 of M phase
The two copies of the chromosome are held together until they are separated during cell division
During mitosis the chromosome condenses very tightly
Chromosome condensation
What is the most basic function of the cell cycle?
replicate the chromosome and then segregate the DNA into genetically identical daughter cells. To do this is also has to make a lot more of the other organelles and stuff in the cell to successfully divide into two cells, so cell growth needs to be coordinated with cell division
What are the main checkpoints in the cell cycle?
The start transition in late G1 isimportant because it is largely regulated by external signals. It needs to make sure the environment is right for division. When this control goes badly, it often can result in cancer.
d) m phase-cytokinesis
d) cytokinesis is part of m phase
How do the protein kinases that control the cell cycle work?
They are always present in the cell, but are switched on and off by phosphorylation.
Cyclins are partly responsible for switching the kinases on and off. They bind to the cell-cycle kinases before the kinases can become active. This is why the kinases are called CDKs (cyclin-dependent protein kinases). Different cyclins control different parts of the cell cycle.
How does the cell cycle control system decide whether or not to move forward?
It allows entry into S phase only if environmental conditions are right, it allows mitosis only if the DNA has been completely replicated, and it initiates chromosome segregation only if the duplicated chromosomes are aligned on the mitotic spindle
c) the kinase activity of the CDK subunit increases at different stages of the cycle
cdk protein levels are constant in the cell cycle, but they are activated by interacting with a series of cyclin proteins that rise and fall at specific cell-cycle stages. Cyclin degradation causes inactivation of the Cdk.
The duplicated chromosomes are correctly aligned on the mitotic spindle
Rb protein
an important negative control for G1. it binds to particular transcription regulators and prevents them from turning on the genes needed for cell proliferation. Mitogens release the Rb brakes by G1 and G1/S cdks to phosphorylate the Rb protein, changing it so that it can’t bind to the transcription regulators.
p53
a transcription regulator that controls the cell’s response to DNA damage, preventing the cell from entering s-phase until the damage hasbeen repaired, or inducing the cell to die if the damage is too extensive. Mutations here are found in about half of all cancers.
It can work at various points in the cell cycle.
For the entry into S-phase, it works by activating the gene that inhibits cdk activity, called p21. p21 binds to G1/S cdk and S-cdk. This gives the cell time to repair DNA damage, or if it is too extensive, drive apoptosis.
d) G1 and G0 phase
S-cdk
activates DNA helicses and recruits DNA synthesis proteins to the replication fork. It also block re-replication by phosphorylating things that prevent the proteins from reloading onto the ORC
M-cdk
Drives entry into mitosis. It is inhibited by phosphorylation. to start mitosis, the phosphates must be removed by cdc25. If DNA replication stalls for some reason, in inhibits cdc25, which prevents removal of the phosphates from m-cdk, which prevents mitosis from happening.
The cdc25/m-cdk loop is a positive feedback loop.
d) s-cdk does not prevent the onset of m-phase. Rather, the inactivation of M-cdk prevents the onset of M phase.
how are chromosomes accurately segregated?
the identical copies of sister chromatids remain tightly bound together by protein complexes called cohesins.
The sister chromatids are tangled up, so to untangle them and prevent damage when they are pulled apart, condensins reorganize and condense them.
cytoskeletal structures in m phase
The mitotic spindle is composed of microtubules and microtubule-associated motor proteins.
The contractile ring consist mostly of actin and myosin filaments.
d) it activates cdc25, which removes the inhibitory phospahtes from M-cdk, activating more m-cdk.
mitotic spindle
rapidly growing and shrinking microtubules (dynamic instability) eventually encounter a chromosome at its kinetochore, where the sister chromatids are pulling apart.
Other microtubules establish the framework of the mitotic spindle and interact with motor proteins.
Astral microtubules radiate outward from the poles and connect with the cell cortex.
Prophase overview
Prometaphase overview
Metaphase overview
Anaphase overview
Begins when the remaining cohesin linkages holding together sister chromatids break apart.
The movements of anaphase are driven by:
1) loss of tubulin subunits on both ends of the kinetochore microtubules (anaphase a)
2) motor proteins (kinesins and dyneins) operating on different spindle microtubules (anaphase b)
Telophase overview
Cytokinesis overview
begins in anaphase, but is not completed until after the two nuclei have been reformed.
cytokinesis in plant cells involves constructing a cell wall between the two cells
kinetochores
protein complex that assembles on the centromere of a condensed mitotic chromosomes; the site to which spindle microtubules attach.
Tension in the kinetochores from being attached to opposite sides of the spindle signals to the kinetochores that they are ready to separate.
Kinetochores that are unattached send a “stop” signal to prevent mitosis from continuing. This is the spindle assembly checkpoint that controls the onset of anaphase.
d) the random growth of microtubules allows for both astral and non-kinetochore microtubules to form.
d)
d) actin and myosin
Survival factors
suppress apoptosis by regulating Bcl2 proteins
c) they promote the expression of cyclin genes, which overcome intracellular braking mechanisms that block entry into the cell cycle
Intrinsic pathway of apoptosis
Depends on the mitochondria and cytochrome C
No real answer given, this is just there to think about
Apoptosis is programmed cell death. The extrinsic pathway for apoptosis is mediated by a ligand-receptor interaction, while the intrinsic pathway depends on mitochondria and the protein cytochrome c
Extrinsic pathway of apoptosis
