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-p21WAF1/CIP1, both targeting Cdk2 but the latter inducing long lasting inactivation. In similarly irradiated S phase cells, however, p21WAF1/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.