A requirement for replication in activation of the ATR-dependent DNA damage checkpoint
A requirement for replication in activation of the ATR-dependent DNA damage checkpoint
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DOI：
10.1101/gad.1013502
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发表时间：
2002-09-15
影响因子：
10.5
通讯作者：
Cimprich, KA
中科院分区：
文献类型：
--
作者：
Lupardus, PJ;Byun, T;Cimprich, KA
使用非洲爪蟾卵提取物系统，我们研究了 DNA 复制在 DNA 损伤检查点激活中的参与情况。我们在此表明，DNA 损伤以不依赖检查点的方式减慢复制，并伴随着复制依赖性 ATR 和 Rad1 向染色质的募集。我们还发现，DNA 损伤后，复制蛋白 RPA 和 Polalpha 在染色质上积聚。最后，当复制受到抑制时，损伤诱导的 Chk1 磷酸化和检查点停滞会被取消。这些数据表明 DNA 损伤检查点的激活需要复制，并提出了 S 期不同损伤 ATR 激活的统一模型。
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.