A requirement for replication in activation of the ATR-dependent DNA damage checkpoint.

ABSTRACT: Using the Xenopus egg extract system, we investigated the involvement of DNA replication in activation of the DNA damage checkpoint. We show here that DNA damage slows replication in a checkpoint-independent manner and is accompanied by replication-dependent recruitment of ATR and Rad1 to chromatin. We also find that the replication proteins RPA and Polalpha accumulate on chromatin following DNA damage. Finally, damage-induced Chk1 phosphorylation and checkpoint arrest are abrogated when replication is inhibited. These data indicate that replication is required for activation of the DNA damage checkpoint and suggest a unifying model for ATR activation by diverse lesions during S phase.

SUBMITTER: Lupardus PJ 

PROVIDER: S-EPMC187437 | biostudies-literature | 2002 Sep

REPOSITORIES: biostudies-literature