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Genes Dev
2002 Sep 15;1618:2327-32. doi: 10.1101/gad.1013502.
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A requirement for replication in activation of the ATR-dependent DNA damage checkpoint.
Lupardus PJ, Byun T, Yee MC, Hekmat-Nejad M, Cimprich KA.
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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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