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how is the cell cycle regulated
cell
what happens if cells at different phases of the cell cycle are fused together
signals in the cytoplasm of the fused cell will cause both nuclei to enter the same phase of the cell cycle
what are the major checkpoints of the cell cycle
G1 checkpoint (before DNA replication)
G2 checkpoint (before mitosis)
M checkpoint (before cytokinesis)
what is the G1 checkpoint
known as restriction point (mammals) / start (yeasts)
most important checkpoint
if cell recieves go ahead signal, usually completes the whole cycle and divides
what is the G0 phase
if no go ahead or stop signal at G1, enter G0 phase
non dividing state, no active cell growth/division
only maintenance
nerve cells, cardiac muscle cells, liver cells are in G0 phase
explain G0 to G1 transition in the liver
most liver cells exist in a reversible G0 phase
liver has capacity to regenerate
prolonged alcohol misuse can reduce this ability
what are cyclins
proteins that regulate progression through checkpoints
levels cyclically change
CDKs activate them
CDK-cyclin active complex phosphorylates downstream targets
what are kinases
enzymes that add a phosphate group to a target protein
aka phosphorylation
what are G1/S cyclins
trigger progression through G1 checkpoint
what are M-cyclins
stimulate entry into mitosis at G2 checkpoint
what are CDKs
levels are constant
activity controlled by cyclic changes in cyclin levels
what regulates CDK regulators
cyclin binding
phosphorylation and dephosphorylation (G2)
binding of inhibitory proteins (G1)
destruction of cyclins - happens at M checkpoint (APC/C)
what happens if DNA damage is present at G1 checkpoint
activates p53, stimulating the transcription of several genes
p21 binds to G1/S-Cdk and S-Cdk and inhibits their activity
blocks entry to S phase
what happens if DNA replication is incomplete at G2 checkpoint
signals inactivate the phosphate Cdc25
blocks dephosphorylation and activation of M-Cdk, blocking entry into mitosis
what happens in the S phase
S-CdK trigger start of DNA replications at each origin
each origin fired once per cell cycle
duplicated sister chromatids are linked together by cohesin
what happens if chromosomes aren’t correctly attached at M checkpoint
“wait” signal → blocks APC/C → blocks sister chromatic separation
cells don’t enter anaphase until all chromosomes are correctly bi-orientated
what triggers the transition from metaphase to anaphase
by protein destruction
what is the APC/C
catalyses ubiquitylation and destruction of:
securin (activates protease that separates sister chromatids)
S and M cyclins
what is P53
trigger apoptosis in cells with damaged DNA = halt damaged cell growth and division
mutations in p53 are found in 70% of lung tumours
what is peto’s paradox
larger animals with more cells don’t have increased cancer risk
suggests they have more effective mechanisms to prevent cancer
elephants have 20 extra copies of the p53 tumour suppressor gene