Lecture 11: Cell cycle Flashcards
Cell divison cycle (4 phases)
G1 phase -> growth and prepareing for S phase
S Phase -> DNA Replication
G2 Phase -> growth and preparing for M phase
M Phase -> mitosis + cytokinesis
varies greatly from one cell type to another
some cells exit the cell cycle and never divide again (i.e. nerve cells -> post-mitotic); some temporarily stop dividing by exiting the G1 phase and entering the G0 phase
challenges facing a dividing cell
must accurately dupliate all its contents, then divide them equally between the two daughter cells
what would happen if a cell tried to divide before its DNA had been replicated
it would be catastrophic as one or both daughter cells would lack part of its genetic material
what would happen if a cell duplicated its DNA but then divide before all its other constituents had doubled
daughter cells would lack some organelles and/or get smaller and smaller
2 major mechanisms control the progression of the cell cycle
- the activity of CDKs -> controls ordering of events in cell cycle
- checkpoints -> ensure one phase is completed before the next begins
levels of M-cyclin/M-Cdk relative to cell cycle stage
Highest at begininng of mitosis; lowest at end of mitosis; increases throughout interphase
which Cdks are associated for G1-S checkpoint (#1) and G2-M checkpoint (#2)?
S-phase: active S-Cdk + S-cyclin
M-phase: active M-Cdk + M-cyclin
G1/S Checkpoint (1)
sufficient nutrients? DNA not damaged? growth signal received? - is environment favorable
point at which cells decide whether to enter the cell cycle based on environmental signals
growth factors (EGF) signal animal cells to proceed through the G1/S checkpoint and enter S-phase
influences cell cycle duration
S-Cdk inhibitor proteins maintain the checkpoint
The checkpoint is satisfied when inhibitor levels are reduced
How do S-Cdk complexes function during checkpoint 1?
If cell cycle is GOOD:
to satisfy the G1/S checkpoint, cells reduce the levels of p27 (inactivates S-Cdk) and other Cdk inhibitors
But cells only do this if conditions are favorable for continuing the cell cycle
if cell cycle is BAD:
p53 is activated and binds to a regulatory region of p21 gene which gets transcribed and translated into a p21 protein which attaches to S-Cdk and inactivates the point S-Cdk
loss of p53 results in more rapid accumulation of mutations as damaged DNA is not repaired (cancer)
G2/M Checkpoint (2)
is all DNA replicated? is all DNA damage repaired?
wee1 kinase enforces the G2/M checkpoint & Cdc25 phosphatase activity satisfies the G2/M checkpoint
Phosphorylation of M-Cdk keeps it inactive
Checkpoint is satisfied when M-Cdk is dephosphorylated
How do M-Cdks function checkpoint 2?
If the cell cycle is GOOD:
Wee1 will add phosphate & then Cdc25 (activating) phosphatase will remove P and activate m-Cdk
if the cell wants to speed up m-Cdk activity, a positive feedback loop will ensue in which Wee1 gets phosphorylated (inactivated), making the inactivator INACTIVE
If the cell cycle is BAD:
Wee 1 (inihibitory kinase) will add P and inactivate m-Cdk
once M-Cdk levels reach a critical threshold concentration, small amounts of active M-Cdk lead to activation of the entire pool of M-Cdk
spindle assembly checkpoint (3)
are all chromosomes properly attached to the mitotic spindle?
M-Cdk remains active at the checkpoint
The checkpoint is satisfied when M-Cyclin is degraded and M-Cdk activity is lost
How does M-Cdk get inactivated during checkpoint 3?
If cell cycle is GOOD:
1) APC/C (protein complex) covalently attaches ubiquitin chain to M-cyclin
2) polyubiquitilation (Creating many ubiquitin chains - marks the protein for destrcution by the proteasome) causes the M-cyclin to degrade, ending the cell cycle
If cell cycle is BAD:
1) No ubiquitin would attach, no degradation of M-cycle, cycle would never end
