Chemical DNA damage activates p21 WAF1/CIP1 ‐dependent intra‐S checkpoint

When cells progressing in G 1 phase are irradiated with UV light, two damage checkpoint pathways are activated: CHK1–Cdc25A and p53–p21 WAF1/CIP1 , both targeting Cdk2 but the latter inducing long lasting inactivation. In similarly irradiated S phase cells, however, p21 WAF1/CIP1 ‐dependent checkpoint is largely inactive. We report here that p21‐dependent checkpoint can effectively be activated and induce a prolonged S phase arrest with similarly extended inactivation of Cdk2 by association of p21 if mid‐S phase cells are damaged with a base‐modifying agent instead of UV light, indicating that the poor utilization of p21‐dependent checkpoint is not an innate property of S phase cells.