Cell Cycle Checkpoints Flashcards
(49 cards)
Coordination between different events of the cell cycle is achieved by …
A system of checkpoints
Function of cell-cycle checkpoints
Prevents entry into the next phase of cell cycle until the events of the preceding phase have been completed
What are the 3 main checkpoints in the cell cycle?
G1 checkpoint (G1-S) G2 checkpoint (G2-M) M-phase checkpoint (metaphase-anaphase)
G1 checkpoint
Monitors the environment before allowing the cell cycle to progress
G2 checkpoint
Monitors the DNA for proper replication & the environment
M-phase checkpoint
Spindle assembly checkpoint (SAC)
Monitors that chromosomes for proper attachment to MTs & for proper alignment at the metaphase plate
What is needed for a cell to grow?
Growth factors
Growth factor, GEF, activates which pathway?
Ras pathway
How is Ras pathway involved in cell growth?
Activated Erk from the Ras pathway targets Cdk4/6
What is the ‘restriction point’ in cell growth?
The point at which cells are committed to entering the S phase and no longer need growth factors
Before restriction point …
growth factors needed
After restriction point …
growth factors not needed as cell is committed to S phase
What is the role of E2F in cell growth?
E2F is a transcription factor in the nucleus that transcribes the genes needed for cells to commit to S phase
What is the role of Rb in cell growth?
A protein that binds to E2F and inhibits it from transcribing genes needed for S phase
What is the role of Cdk4/6 in cell growth?
Once activated by Erk, they phosphorylate Rb which causes it to unbind from E2F
What is the effect of E2F not being blocked in cell growth?
Key S phase protein are expressed and the restriction point reached
What happens if the cell does not commit to S phase?
It enters a specialised state - G0 state
What is G0 state?
Cells can enter a non-dividing state in which they can remain in for a long period of time until signalled to emerge
What is the effect of DNA damage on the cell cycle?
DNA damage can arrest the cell cycle in G1 phase
What effect does inducing p21 have on the cell cycle?
p21 binds to and inhibits complexes of cyclin-cdk. In G1, this prevents phosphorylation of Rb so the cell remains in G1
Generally, it can bind to main cellular Cdks and block cell cycle at multiple stages
What effect does inducing Puma have on the cell cycle?
Puma inhibits Bcl2, a key protein that inhibits cell death. So, inducing Puma will allow cell death to happen
What is the role of p53 in cancer?
p53 is inactivated therefore cell cycle arrest and apoptosis are inhibited so unrestrained replication of damaged DNA leads to high rate of mutations that tend to become cancerous
How does DNA damage prevent cells from entering M phase?
DNA damage activates ATR which activates Chk1 which phosphorylates and inactivates Cdc25 therefore cyclin B-Cdk1 is not activated
What are mitogens?
Signals that stimulate cells to divide