The radiation-induced S-phase checkpoint is independent of CDKN1A

We recently demonstrated that, in response to radiation, replication is dow n-regulated at the level of individual origins throughout S phase of the ce ll cycle. Since several in vitro studies demonstrate that CDKN1A (formerly known as p21) down-regulates replication by inhibiting PCNA, and since CDKN 1A can retard progression of cells through S phase in vivo, the question ar ises whether CDKN1A is involved in the S-phase damage-sensing pathway. In t he present study we analyzed the effect of ionizing radiation on CDKN1A(+/) and CDKN1A(-/-) cells derived from the HCT 116 cell line. Neither progres sion of cells through S phase nor survival after exposure to ionizing radia tion is influenced by CDKN1A status in either synchronous or asynchronous c ells. These results establish that CDKN1A is not necessary for the acute S- phase damage-sensing pathway that functions to prevent firing of replicatio n origins during S phase. (C) 1999 by Radiation Research Society.