Fig. 8. Model of transcriptional repression and G2 arrest. A pathway involving ATM, ATR, CHK1 and CHK2 inactivates CDC25C in response to DNA damage, leaving the CDK1/Cyclin B1 complex inactive. p53 also helps to inactivate CDK1 by inducing p21/WAF1, GADD45 and 14-3-3. Cells blocked by these pathways are in G2, with high levels of all the proteins needed for mitosis. The block can be overcome by simple re-activation of CDK1. p53 also utilizes p21/WAF1 to block the phosphorylation of RB-family proteins by CDKs other than CDK1. Hypophosphorylated RB bound to E2F then downregulates the levels of proteins needed for mitosis. The similarity of this effect to the changes in gene expression that occur during G0 suggests that the p53/RB-dependent pathway drives cells out of the cell cycle from G2.