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Ataxia-telangiectasia Mutated (ATM)-dependent Activation of ATR Occurs through Phosphorylation of TopBP1 by ATM

Yoo, Hae Yong and Kumagai, Akiko and Shevchenko, Anna and Shevchenko, Andrej and Dunphy, William G. (2007) Ataxia-telangiectasia Mutated (ATM)-dependent Activation of ATR Occurs through Phosphorylation of TopBP1 by ATM. Journal of Biological Chemistry, 282 (24). pp. 17501-17506. ISSN 0021-9258. https://resolver.caltech.edu/CaltechAUTHORS:YOOjbc07

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1074/jbc.M701770200DOIUNSPECIFIED
ORCID:
AuthorORCID
Kumagai, Akiko0000-0003-2422-8053
Dunphy, William G.0000-0001-7598-8939
Additional Information:© 2007 the American Society for Biochemistry and Molecular Biology. Received for publication, February 28, 2007 , and in revised form, April 17, 2007. Originally published In Press as doi:10.1074/jbc.M701770200 on April 19, 2007. This work was supported by National Institutes of Health Grants GM070891 and GM043974 (to W.G.D.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1.
Funders:
Funding AgencyGrant Number
NIHGM070891
NIHGM043974
Issue or Number:24
Record Number:CaltechAUTHORS:YOOjbc07
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:YOOjbc07
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8422
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:03 Aug 2007
Last Modified:09 Mar 2020 13:18

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