lec 1. cell cycle Flashcards
mitogens
signals that induce cell to begin cell division
growth factors
extracellular signals that control D-type cyclins and drive the G1 phase
G0
quiescent state where cell does not proliferate
G1 Phase
cell grows in size
cyclin D + Cdk4/6 (G1-Cdk)
Restriction Point Cdk complex
cyclin E + Cdk 2 (G1/S-Cdk)
S Phase
replicate DNA
cyclin A + Cdk2
cyclin A + Cdk1/Cdc2 (S-Cdk)
G2 Phase
grow, prepare to divide
cyclin A + Cdk1/Cdc2 (S-Cdk)
M phase
mitosis
cyclin B + Cdk1/Cdc2 (M-Cdk)
how the cell cycle is controlled
through levels of cyclins/Cdks and checkpoints
Cyclin control of cell cycle
cyclins are controlled by intracellular signals except for D-types which are controlled by extracellular and tell cell whether it should cross restriction point and start proliferating
complexes are also regulated by CKIs which allow cell cycle to move in one direction
CDK inhibitors (CKIs)
regulate cyclin/Cdk complexes
- activate complex in next phase, inhibit complex in previous phase
INK family acts on D-type
p57, p27, p21 act on cyclins E, A, B
3 checkpoints in cell cycle
1) G1/S restriction point
2) G2/M checkpoint
3) metaphase/anaphase checkpoint
restriction point
At G1/S:
D + Cdk 4 hypophosphorylate E2F. E cyclin dissociates E2F which then transcribes gene to send cell into S-phase
3 places where DNA damage is spotted
1) G1
2) entry into S
3) entry into mitosis
chromosome non-disjunction
failure of homologous or sister chromatids to separate correctly
how radiation causes DNA damage
it breaks DNA which activates ATM/ATR, and Chk1/Chk2 kinases which activate p53 and then turn on p21 which inactivates G1/S-Cdk and S-Cdk
2 problems with DNA replication
1) DNA has to be replicated accurately
2) DNA must only be copied once
licensing
inactive helicases are put onto replication origins to form a PreRC in G1, and then are activated by S-Cdk -> this ensures DNA is replicated once
differences in cell cycle during development
cyclins E and A maintain high levels in the wrong place. As a result, Rb is hyperphosphorylated which drives a short G1, and CKIs are expressed at low levels.
DNA repair in G1 and G2
G1: non-homologous end joinging
G2: homologous recombination
