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Four phases of the cell cycle
Cyclins and CDKs related to each phase?
G1 (early): D-CDK 4/6
- G1 (late): E-CDK 2
- S: A-CDK 2
- S/G2: A-Cdc2/CDK 1
- M: B-Cdc2/CDK 1
How do cyclins and CDKs function
- specific Cyclins will activate specific CDKs
- Cyclins are created when needed
- CDKs have no function w/o cyclin
What are the two regulation levels of CDK targets?
- 1) high phosphorylation
- 2) high phosphotase activity
What are the three cell cycle checkpoints?
- 1) Restriction point (G1): cyclin D-CDK4/6
- 2) G2/M checkpoint: cyclin B-CDK1 (cdc2
- 3) M checkpoint: cyclin B-CDK1 (cdc2)
What is the process of activating CyclinD-CDK4/6?
Mitogen - MAP kinase - MYC transcription factor - cyclin D
what are the two cell types that get trapped in G0 ?
How does the cell cycle pass the 1st checkpoint?
- 1st checkpoint = Restriction Point
- D-CDK4/6 + E-CDK2 hyperphosphorylate Rb (E cannot work unless Rb is all ready phospho. by D)
- Rb disassociates from E2F
- E2F binds to DNA to transcribe necessary proteins
What is the importance of the G2/M and M checkpoints?
Checks for correct DNA pairing and haults to repair any damage
What is the original name for the B-cdc2(CDK1) complex?
MPF - maturation promoting factor
How is the B-cdc2 complex inactivated and activated?
- Inactivated: cdc2 is phospho.
- Activated: when DNA synthesis has been approved and corrected, the two inactivation phospho. are released by cdc25 phosphotase and the one activation phospho. stays on. MPF now has full activity.
How do sister chromatids separate in the M-phase?
- APC binds to Securin to release Separase which will cut cohesions b/t the sister chromatids
- APC also degrades cyclinB, which inactivates cdc2(CDK1)
What are the two CDK-inhibtors and what do they inhibit?
- INK4: CDK4/6
- WAF1/CIP1 (and p21): all others CDKs except 4/6
When is p21 and p16 activated for inactivation?
- P21: DNA damage (starts at restriction site)
- P16: environmental stress (G1)
Why is P21 so important?
It works on the E-CDK2 complex at the restriction checkpoint so Rb is not phosphorylated