Lecture 15

Question 1

What does cyclin expression require?

Answer 1

Mitogen dependent signalling

Question 1

How does mitogen dependent signalling work?

Answer 1

1. Cell receives signals from adjacent cell or mitogen
2. Extracellular signals mediated from membrane associated receptors to nucleus
3. MAPKK activated - Myc activated for transcription

Question 2

CDK regulation in G1 and S-phase

Answer 2

Myc promotes cyclin D and E2F expression

E2F is transcriptional regulator of S-phase genes and cyclin E/A

Question 3

Explain CDK activity regulation

Answer 3

CDK inactive

Partly active when CDK binds cyclin to form T-loop

Fully activated by CAK with activating phosphate

Question 4

What do CDK inhibitors do?

Answer 4

• CDKi binds SPF - prevents S-phase entry
• CDK binds cyclin and CDK subunits
• Cyclin-CDK complex inactive - prevents substrate binding and phosphorylation
• Transition into S-phase requires CDK inhibitor degradation

Question 5

Cyclin dependent kinases drive cell cycle progression

Answer 5

• Cyclin levels accumulate, then drop
• Cyclins degraded by proteasome
• Sequential cyclin expression increases CDK activity
• Increase in CDK regulates key cell cycle transitions

DNA replication controlled by distinct CDK activity thresholds

Question 6

Regulation of DNA replication by oscillating Cdk activity

Answer 6

• Initiation occurs once per cell cycle
• DNA rep must go to completion
• Cells utilize multiple origins to ensure timely completion of DNA replication
• ORC associates with DNA in mitosis
• High CDK prevents DNA replication