Cell Cycle Flashcards
how is the genetic content different between G1 and G2?
G1- 2C- one maternal and one paternal set. G2- 4C- each has been replicated
describe the two different states of G0
quiescent- remain the potential to re-enter the cell cycle. senescent- terminally differentiated cells that have lost the ability to divide
what is the START transition?
the G1-S transition. After going through this transition commits the cell to a full cycle.
how does CDK concentration fluctuate throughout the cell cycle
relatively constant
activity of cyclin CDK complexes is both necessary and sufficient to move through the cell cycle
ok
describe the 5 mechanisms that control kinase activity
- Cyclin association.
- Phosphorylation- the complexes have an inhibitory and an activation position
- Cdc 25 removes the inhibitory phosphorylation
- Cyclin kinase inhibitors- bind to Cdk or Cdk complexes and inhibit activity
- Cyclin subunit proteolysis- cyclin gets ubiquinated and destroyed at different parts of the cell cycle
what are the 2 different families of cyclin kinase inhibitors
Ink4 family and CKI family
what are the two proteolytic enzymes for ubiquitinizing cyclins
APC/C- ubiquitin ligase in m-phase. SCF- ubiquitin ligase for all other cycles
describe the regulation of the START phase of the cell cycle
controlled by Rb protein. when unphosphorylated, binds to E2F, inhibiting it. At the end of G1, cyclin D accumulates and activates CDK4 and CDK6, which phosphorylate Rb, causing it to release E2F, which is a transcriptional activator
Describe regulation of the s-phase; why does replication only occur once?
Origin replication complex associates with replication origins throughout. Cdc6 binds to ORC and recruits MCM. ORC, Cdc6, and MCM get phosphorylated via CDK-cyclin A and Cdc7-Dbf4 kinases. Reinitiation is prevented by ubiquitization of cdc6 via SCF.
What controls entering into Mitosis
cyclin B/cdk activity- important for nuclear envelope breakdown, chromosome condensation, and spindle assembly
what controls exiting mitosis
anaphase promoting complex- ubiquinates protein scaffolding holding together sister chromatids and then ubiquitinates cyclin b
what are the 4 major checkpoints in the cell cycle?
G1- arrests d/t DNA damage. p53 regulates this
S- arrests d/t unreplicated DNA
G2- arrests d/t DNA damage
M- arrests d/t improper spindle assembly
describe the p53 mechanism
normally binds to Mdm2 which ubiquitinizes it and gets degraded. when DNA is damaged, ATM/ATR or Chk1/2 phosphorylate p53 so that it cannot bind to Mdm2. instead, it acts as a transcription activator for cyclin kinase inhibitor p21, which inhibits cyclin E CDK, preventing the cell from moving forward in the cell cycle
describe the spindle checkpoint
if no microtubules bind the kinetochore, the complex of bub1, bub3, and mad1 phosphorylate Mad2. Mad2 binds to the APC inhibiting it, preventing anaphase.
