HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 24, 17501-17506, June 15, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/24/17501    most recent M701770200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yoo, H. Y. Articles by Dunphy, W. G. Search for Related Content PubMed PubMed Citation Articles by Yoo, H. Y. Articles by Dunphy, W. G. Social Bookmarking                      What's this?

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

Hae Yong Yoo, Akiko Kumagai, Anna Shevchenko, Andrej Shevchenko, and William G. Dunphy¹

From the Division of Biology 216-76, California Institute of Technology, Pasadena, California 91125 and Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany

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.

Received for publication, February 28, 2007 , and in revised form, April 17, 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.

¹ To whom correspondence should be addressed. Tel.: 626-395-8433; Fax: 626-795-7563; E-mail: dunphy{at}cco.caltech.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Y. Yoo, A. Kumagai, A. Shevchenko, A. Shevchenko, and W. G. Dunphy The Mre11-Rad50-Nbs1 Complex Mediates Activation of TopBP1 by ATM Mol. Biol. Cell, May 1, 2009; 20(9): 2351 - 2360. [Abstract] [Full Text] [PDF]

				B. Shiotani and L. Zou ATR signaling at a glance J. Cell Sci., February 1, 2009; 122(3): 301 - 304. [Full Text] [PDF]

				D. A. Mordes, E. A. Nam, and D. Cortez Dpb11 activates the Mec1-Ddc2 complex PNAS, December 2, 2008; 105(48): 18730 - 18734. [Abstract] [Full Text] [PDF]

				M. Hitomi, K. Yang, A. W. Stacey, and D. W. Stacey Phosphorylation of Cyclin D1 Regulated by ATM or ATR Controls Cell Cycle Progression Mol. Cell. Biol., September 1, 2008; 28(17): 5478 - 5493. [Abstract] [Full Text] [PDF]

				A. E. Burrows and S. J. Elledge How ATR turns on: TopBP1 goes on ATRIP with ATR Genes & Dev., June 1, 2008; 22(11): 1416 - 1421. [Abstract] [Full Text] [PDF]

				D. A. Mordes, G. G. Glick, R. Zhao, and D. Cortez TopBP1 activates ATR through ATRIP and a PIKK regulatory domain Genes & Dev., June 1, 2008; 22(11): 1478 - 1489. [Abstract] [Full Text] [PDF]

				A. Kulkarni and K. C. Das Differential roles of ATR and ATM in p53, Chk1, and histone H2AX phosphorylation in response to hyperoxia: ATR-dependent ATM activation Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L998 - L1006. [Abstract] [Full Text] [PDF]

				Y.-W. Zhang, Z.-X. Zhang, Z.-H. Miao, and J. Ding The Telomeric Protein TRF2 Is Critical for the Protection of A549 Cells from Both Telomere Erosion and DNA Double-Strand Breaks Driven by Salvicine Mol. Pharmacol., March 1, 2008; 73(3): 824 - 832. [Abstract] [Full Text] [PDF]

				J. Lee, A. Kumagai, and W. G. Dunphy The Rad9-Hus1-Rad1 Checkpoint Clamp Regulates Interaction of TopBP1 with ATR J. Biol. Chem., September 21, 2007; 282(38): 28036 - 28044. [Abstract] [Full Text] [PDF]