What are the phases of the cell cycle?
M -> G1 -> S -> G2
What happens in G1?
Preparation for DNA replication
What happens in S phase?
What happens in G2?
Preparation for mitosis
Describe the chromosomes in each stage of the cell cycle
- In G1, 2N (diploid)
- In S, replication, so 2N -> 4N
- In G2, 4N (tetraploid)
- In mitosis, 4N -> 2N
Describe the transitions between phases in the cell cycle?
They occur in an orderly fashion
What are the key regulators of the transitions between different stages in the cell cycle?
Cyclin dependant kinases (CDKs)
What are CDKs?
What do serine/theonine kinases do?
Phosphorylate substrates at SER/THR-PRO-X-LYS/ARG motifs
What do the CDK substrates do?
Promote cell cycle progression
When are CDKs active?
When they are bound by their partners cyclins
How do CDK protein levels vary during the cell cycle?
They are mainly stable
What happens to cyclin levels during the cell cycle?
They rise and fall
What is the result of the rising and falling of cyclin levels during the progression of the cell cycle?
Activation of CDK oscillates
Does CDK or cyclin dictate the progression of the cell cycle?
Cyclin, as its levels are rising and falling
What CDKs operate during G1?
What cyclins are involved in the G1 phase of the cell cycle?
Cyclin D1, D2, and D3
What CDKs are involved in the G1/S phase of the cell cycle?
What cyclins are involved in the G1/S phases of the cell cycle?
Cyclin E1, E2
What CDKs are involved in the S phase of the cell cycle?
What cyclins are involved in the S phase of the cell cycle?
Cyclin A1, A2
What CDKs are involved in the M phase of the cell cycle?
What cyclins are involved in the M phase of the cell cycle?
What cyclins and CDKs are essential for entry into G1?
What cyclins and CDKs regulate G1 to S progression?
What cyclins and CDKs are required during S and G2 phases
What do cyclinA/CDK2 do during S and G2 phases?
Triggers DNA polymerase activity
What cyclins and CDKs promote entry into mitosis?
What is RB?
A tumour supressor gene
How does RB act as a tumour suppressor gene?
Rb binds to E2F, which inhibits it from transcribing its S-phase genes
What are the S phase genes produced by E2F responsible for?
- DNA synthesis
- DNA replication
- DNA repair
- Regulation (via Cyclin E and Cyclin A)
What cyclin/CDK complex activates RB?
Cyclin D and CDK4/6
How is Rb inactivated?
Phosphorylation by cyclinE/CDK2
What regulates phosphorylation of Rb by cyclinE/CDK2?
What effect does the HPV virus have on Rb?
It produces the E7 protein, which binds and inactivated Rb
What acts as negative regulation of the cyclinD and CDK4/6 complex?
INK4 (INhibitor of Kinase 4)
What produces the INK4 complexes?
- p16 produces INK4a
- p15 produces INK4b
- p18 produces INK4c
- p19 produces INK4d
How do the INK complexes act as negative regulators of CDK4?
They bind CDK, and block interaction with cyclin so the complex cannot form and therefore it cannot be activated
What factors act as positive regulation CDK4?
- Growth factor
- Myc oncogene
What acts as a negative regulator for cyclinE/CDK2?
CDK-interacting protein (CIP) or kinase inhibitor protein (KIP)
What produces the CIP and KIP proteins?
- p21 produces CIP1
- p27 produces KIP1
- p57 produces KIP2
What are the stages of mitosis?
What is the most important phase of mitosis to be regulated?
Prophase -> metaphase
Why is it important to regulate prophase -> metaphase?
Because there is no way back after metaphase
What promotes entry into M phase?
What is essential for M phase progression into metaphase?
What does CDK1 do?
Phosphorylates substrates involved in;
- Nuclear envelope breakdown
- Chromosome condensation
- Mitotic spindle assembly
What are cyclinA/B and CDK1 targets of?