Ataxia-telangiectasia mutated (ATM)-dependent activation of ATR occurs through phosphorylation of TopBP1 by ATM

被引：92

作者：

Yoo, Hae Yong

Kumagai, Akiko

Shevchenko, Anna

Shevchenko, Andrej

Dunphy, William G. ^{[1
]}

机构：

[1] CALTECH, Div Cell Biol, Pasadena, CA 91125 USA

[2] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2007年 / 282卷 / 24期

关键词：

D O I：

10.1074/jbc.M701770200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

ATM ( ataxia-telangiectasia mutated) is necessary for activation of Chk1 by ATR ( ATM and Rad3-related) in response to double-stranded DNA breaks ( DSBs) but not to DNA replication stress. TopBP1 has been identified as a direct activator of ATR. We show that ATM regulates Xenopus TopBP1 by phosphorylating Ser-1131 and thereby strongly enhancing association of TopBP1 with ATR. Xenopus egg extracts containing a mutant of TopBP1 that cannot be phosphorylated on Ser-1131 are defective in the ATR-dependent phosphorylation of Chk1 in response to DSBs but not to DNA replication stress. Thus, TopBP1 is critical for the ATM-dependent activation of ATR following production of DSBs in the genome.

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收藏

页码：17501 / 17506

页数：6

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