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XB-ART-35795
J Biol Chem 2007 Jun 15;28224:17501-6. doi: 10.1111/j.1467-2995.2006.00316.x.
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Ataxia-telangiectasia mutated (ATM)-dependent activation of ATR occurs through phosphorylation of TopBP1 by ATM.

Yoo HY , Kumagai A , Shevchenko A , Shevchenko A , Dunphy WG .


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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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Species referenced: Xenopus laevis
Genes referenced: antxr1 atm atr chek1 topbp1