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

被引：140

作者：

Lupardus, PJ ^{[1
]}

Byun, T ^{[1
]}

Yee, MC ^{[1
]}

Hekmat-Nejad, M ^{[1
]}

Cimprich, KA ^{[1
]}

机构：

[1] Stanford Univ, Dept Mol Pharmacol, Stanford, CA 94305 USA

来源：

GENES & DEVELOPMENT | 2002年 / 16卷 / 18期

关键词：

ATR; Rad1; DNA damage; Xenopus; checkpoint; replication;

D O I：

10.1101/gad.1013502

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：2327 / 2332

页数：6

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