A Requirement for Replication in Activation of the ATR-dependent DNA Damage Checkpoint

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2002 Sep 17

PMID 12231621

Citations 69

Authors

Patrick J Lupardus

Tony Byun

Muh-Ching Yee

Mohammad Hekmat-Nejad

Karlene A Cimprich

Affiliations

Soon will be listed here.

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.

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