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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

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

Lupardus Patrick J PJ   Byun Tony T   Yee Muh-Ching MC   Hekmat-Nejad Mohammad M   Cimprich Karlene A KA  

Genes & development 20020901 18


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 replica  ...[more]

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