L3: Cell Signalling and the Cell Cycle in Cancer

Question 1

Which cell cycle phase is responsive to mitogens?

Answer 1

G1 phase

Question 2

What are the phases of the cell cycle?

Answer 2

• G0
• G1
• S
• G2
• M

Question 3

Which phase of the cell cycle is responsive to mitogens?

Answer 3

G1 phase

Question 4

Which is the quiescence state?

Answer 4

Non-dividing (resting) state is G0

Question 5

What are the features of G1 phase?

Answer 5

Growth phase 1, cell growth and preparation for DNA synthesis
- responsive to environmental signals
- contains G1 resitriction checkpoint (R)
- G1/S DNA damage checkpoint

Question 6

What are the features of S phase?

Answer 6

Synthesis phase, DNA replication

Question 7

What are the features of G2 phase?

Answer 7

GRowth phase 2, preparation for mitosis, checkpoint for DNA damage before entering M phase

Question 8

What happens during M phase?

Answer 8

mitosis, nuclear division

Question 9

How is the cell cycle regulated? Explain using relevant cyclins and CDKs

Answer 9

• In G1 phase, we’ve got favourable conditions: increased expression of cyclin D (inhibits the cell cycle exit); cyclin D then binds to CDK 4/6 (can be oncogenic, often amplified in cancers); this then drives expression of cyclin E; makes a complex with CDK2 and inhibits the retinoblastoma gene product
• In S phase, E2F then drives the conversion of Cyclin E to A, which drives cells into the S phase
• In G2 phase: eventually then leaves CDK2 conversion to CDK1
• In M phase: cyclin A is converted to Cyclin B

Question 10

What are the checkpoints and where in the cell cycle are they located?

Answer 10

• In the G1 phase CDK4/6 and cyclin D complex, DNA damage inhibits this complex formation, pauses cell cycle, if can’t repair cells become quiescent or senescent (irreversibly go out of cell cycle); similar with CDK2 and Cyclin E/A complex
• In S phase: replication stress checkpoint, damage here leads to apoptosis because it’s a very complicated process
• In M phase: spindle checkpoint, defects lead to apoptosis – in cancer many of these are dysregulated