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

J. Biol. Chem., Vol. 281, Issue 20, 13861-13864, May 19, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/20/13861    most recent C600051200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Raynard, S. Articles by Sung, P. Search for Related Content PubMed PubMed Citation Articles by Raynard, S. Articles by Sung, P. Social Bookmarking                      What's this?

A Double Holliday Junction Dissolvasome Comprising BLM, Topoisomerase III, and BLAP75^*

Steven Raynard¹, Wendy Bussen¹, and Patrick Sung²

From the Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520 and the Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center, San Antonio, Texas 78245

Bloom syndrome (BS), an autosomal recessive disorder, is marked by a high incidence of cancer early in life. Cells derived from BS patients are unstable genetically and exhibit frequent sister chromatid exchanges, reflective of homologous recombination (HR) deregulation. BLM, the RecQ-like helicase mutated in BS, is found in several cellular protein complexes, all of which contain topoisomerase III (Topo III) and a novel protein BLAP75. Here, using highly purified human proteins, we show that BLAP75 associates independently with both Topo III and BLM. Even though BLM and Topo III can dissolve the double Holliday junction (DHJ) to yield non-crossover recombinants (1), under physiological conditions, DHJ dissolution becomes completely dependent on BLAP75. The effect of BLAP75 on BLM-Topo III is highly specific, as it is not seen with the combination of Topo III and Escherichia coli RecQ helicase or another human RecQ-like helicase WRN. Thus, BLM, Topo III, and BLAP75 constitute a dissolvasome complex that processes HR intermediates to limit DNA crossover formation. This function of the BLM-Topo III-BLAP75 dissolvasome is likely indispensable for genome maintenance and cancer avoidance.

Received for publication, March 3, 2006 , and in revised form, March 29, 2006.

Addendum—A paper with similar findings by Wu et al. (15) appeared while our manuscript was undergoing peer review.

^* This work was supported by National Institutes of Health Research Grants RO1GM57814 and RO1CA110415 and United States Department of Defense Predoctoral Fellowships W81XWH-04-1-0410 and DAMD17-03-1-0586. 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.

¹ These two authors have contributed equally to this study.

² To whom correspondence should be addressed: Dept. of Molecular Biophysics and Biochemistry, Yale University School of Medicine, 333 Cedar St., C130 Sterling Hall of Medicine, New Haven, CT 06520. Tel.: 203-785-4553; Fax: 203-785-6404; E-mail: Patrick.Sung{at}yale.edu.

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

This article has been cited by other articles:

				S. Raynard, W. Zhao, W. Bussen, L. Lu, Y.-Y. Ding, V. Busygina, A. R. Meetei, and P. Sung Functional Role of BLAP75 in BLM-Topoisomerase III{alpha}-dependent Holliday Junction Processing J. Biol. Chem., June 6, 2008; 283(23): 15701 - 15708. [Abstract] [Full Text] [PDF]

				H. Lu, J. Yue, X. Meng, J. A. Nickoloff, and Z. Shen BCCIP regulates homologous recombination by distinct domains and suppresses spontaneous DNA damage Nucleic Acids Res., December 18, 2007; 35(21): 7160 - 7170. [Abstract] [Full Text] [PDF]

				D. Branzei and M. Foiani RecQ helicases queuing with Srs2 to disrupt Rad51 filaments and suppress recombination Genes & Dev., December 1, 2007; 21(23): 3019 - 3026. [Full Text] [PDF]

				D. V. Bugreev, X. Yu, E. H. Egelman, and A. V. Mazin Novel pro- and anti-recombination activities of the Bloom's syndrome helicase Genes & Dev., December 1, 2007; 21(23): 3085 - 3094. [Abstract] [Full Text] [PDF]

				Y. Hu, S. Raynard, M. G. Sehorn, X. Lu, W. Bussen, L. Zheng, J. M. Stark, E. L. Barnes, P. Chi, P. Janscak, et al. RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments Genes & Dev., December 1, 2007; 21(23): 3073 - 3084. [Abstract] [Full Text] [PDF]

				W. Bussen, S. Raynard, V. Busygina, A. K. Singh, and P. Sung Holliday Junction Processing Activity of the BLM-Topo III{alpha}-BLAP75 Complex J. Biol. Chem., October 26, 2007; 282(43): 31484 - 31492. [Abstract] [Full Text] [PDF]

				M. Otsuki, M. Seki, E. Inoue, A. Yoshimura, G. Kato, S. Yamanouchi, Y.-i. Kawabe, S. Tada, A. Shinohara, J.-i. Komura, et al. Functional interactions between BLM and XRCC3 in the cell J. Cell Biol., October 8, 2007; 179(1): 53 - 63. [Abstract] [Full Text] [PDF]

				H. W. Mankouri, H.-P. Ngo, and I. D. Hickson Shu Proteins Promote the Formation of Homologous Recombination Intermediates That Are Processed by Sgs1-Rmi1-Top3 Mol. Biol. Cell, October 1, 2007; 18(10): 4062 - 4073. [Abstract] [Full Text] [PDF]

				C.-F. Chen and S. J. Brill Binding and Activation of DNA Topoisomerase III by the Rmi1 Subunit J. Biol. Chem., September 28, 2007; 282(39): 28971 - 28979. [Abstract] [Full Text] [PDF]

				V. A. Rao, C. Conti, J. Guirouilh-Barbat, A. Nakamura, Z.-H. Miao, S. L. Davies, B. Sacca, I. D. Hickson, A. Bensimon, and Y. Pommier Endogenous {gamma}-H2AX-ATM-Chk2 Checkpoint Activation in Bloom's Syndrome Helicase Deficient Cells Is Related to DNA Replication Arrested Forks Mol. Cancer Res., July 1, 2007; 5(7): 713 - 724. [Abstract] [Full Text] [PDF]