ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks
ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks
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DOI：
10.1038/ncb1337
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发表时间：
2006-01-01
影响因子：
21.3
通讯作者：
Jackson, SP
中科院分区：
文献类型：
--
作者：
Jazayeri, A;Falck, J;Jackson, SP
通常认为DNA损伤检查点激酶、共济失调-毛细血管扩张突变（ATM）和ATM-和Rad 3-相关（ATR）相互独立地起作用。在这里，我们表明，ATM和减数分裂重组11（Mre 11）的核酸酶活性是DNA双链断裂（DSB）的加工所必需的，以产生ATR募集和随后的磷酸化和Chk 1激活所需的复制蛋白A（RPA）包被的ssDNA。此外，我们表明，有效的ATM依赖性ATR激活响应DSB仅限于S和G2细胞周期阶段，需要CDK激酶活性。因此，在对DSB的应答中，ATR活化以细胞周期依赖性方式由ATM调节。
It is generally thought that the DNA- damage checkpoint kinases, ataxia- telangiectasia mutated ( ATM) and ATM- and Rad3-related ( ATR), work independently of one another. Here, we show that ATM and the nuclease activity of meiotic recombination 11 ( Mre11) are required for the processing of DNA double- strand breaks ( DSBs) to generate the replication protein A ( RPA)- coated ssDNA that is needed for ATR recruitment and the subsequent phosphorylation and activation of Chk1. Moreover, we show that efficient ATM- dependent ATR activation in response to DSBs is restricted to the S and G2 cell cycle phases and requires CDK kinase activity. Thus, in response to DSBs, ATR activation is regulated by ATM in a cell- cycle dependent manner.