12.1. The Cell Cycle

Question 1

Cell division (proliferation)…

Answer 1

Interphase (a preparatory phase):
- Gap 0 (G0): quiescence: a phase cells enter when they temporarily exit the cell cycle (they retain the ability to reenter if they receive the correct stimuli).
- Gap 1 (G1): cells increase in size and prepare themselves to enter the next phase.
- S: DNA is replicated here to ensure the two daughter cells inherit a full copy of DNA.
- Gap 2 (G2): cells prepare themselves for undergoing the final steps of mitosis and cytokinesis.

Question 2

Cyclins and cyclin-dependent kinases…

Answer 2

Cyclin-dependent kinases power the cell cycle.

The activity of these protein kinases is regulated by cyclins.

CDK on its own cannot do anything. When cyclin binds, it changes CDK exposing its active site.

A protein substrate and ATP bind to CDK. The protein substrate is phosphorylated.

The phosphorylated protein regulates the cell cycle.

Question 3

Cyclin-CDK complexes drive cell cycle progression…

Answer 3

There are four CDK proteins.

There are four cyclins.

These give rise to six cyclin-CDK complexes.

Cyclin levels fluctuate during the cell cycle, with different ones peaking at different points to control the cycle.

Question 4

Cyclin-CDK complexes…

Answer 4

CDK1 + cyclin A –> G2 to M phase transition.
CDK1 + cyclin B –> M phase.
CDK2 + cyclin E –> G1 to S phase transition.
CDK2 + cyclin A –> S phase.
CDK4 + cyclin D –> G1 phase.
CDK6 + cyclin D –> G1 phase.

Question 5

Checkpoints

Answer 5

End of G1: a restriction point that checks the cell size, if the conditions are favourable and if DNA damage has occured.

During G2: checks for damaged or unduplicated DNA and unduplicated chromosomes.

End of M: checks for chromosome attachment to the mitotic spindle.

Question 6

Tumours…

Answer 6

If a cell becomes defective in its signalling machinery, it may enter the cell cycle permanently, giving rise to identical defective daughter cells.

Cancer drugs target this cell cycle:
- Etoposide inhibits growth factor stimulation to prevent the cell proceeding from G1.
- 5-fluorouracil blocks DNA replication.
- Radiation damages DNA and causes apoptosis at the S and G2 checkpoints.
- Taxol blocks the mitotic spindle during mitosis.