43 Cell cycle arrest

Questions

Why is cell cycle arrest important?

What are the main mechanisms of DNA repair?

How may errors in cell cycle arrest lead to cancer?

The cell cycle may be arrested at two points (G₁–S and G₂–M) as a result of DNA damage (Figs 3.43.1 and 3.43.2). Mechanisms of cell cycle arrest involve inhibition of regulation of cyclin-dependent protein kinases (CDKs) by phosphorylation or CDK inhibitors. For example, the tumour suppressor gene product p53 is important in arresting the cell cycle at G_1, thereby preventing the replication of damaged DNA, and it may stimulate DNA repair indirectly. Expression of p53 is normally low but is increased dramatically when cell DNA is damaged, leading to the suggestion that it is a ‘guardian of the genome’. p53 induces the expression of the CDK inhibitor p21, which inhibits G₁–S CDK.

Fig. 3.43.1 Arrest of the cell cycle at G₂–M. CDK, cyclin-dependent protein kinase.

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