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J. Biol. Chem., Vol. 283, Issue 18, 12166-12174, May 2, 2008

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Molecular Anatomy of the Recombination Mediator Function of Saccharomyces cerevisiae Rad52^*

Changhyun Seong¹, Michael G. Sehorn², Iben Plate, Idina Shi, Binwei Song^¶3, Peter Chi, Uffe Mortensen, Patrick Sung, and Lumir Krejci^||14

From the Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, the Center for Microbial Biotechnology, BioCentrum-DTU, Technical University of Denmark, DK-2800 Lyngby, Denmark, the ^¶Institute of Biotechnology and Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texac 78245, and the ^||National Center for Biomolecular Research, Masaryk University, Brno 62500, Czech Republic

A helical filament of Rad51 on single-strand DNA (ssDNA), called the presynaptic filament, catalyzes DNA joint formation during homologous recombination. Rad52 facilitates presynaptic filament assembly, and this recombination mediator activity is thought to rely on the interactions of Rad52 with Rad51, the ssDNA-binding protein RPA, and ssDNA. The N-terminal region of Rad52, which has DNA binding activity and an oligomeric structure, is thought to be crucial for mediator activity and recombination. Unexpectedly, we find that the C-terminal region of Rad52 also harbors a DNA binding function. Importantly, the Rad52 C-terminal portion alone can promote Rad51 presynaptic filament assembly. The middle portion of Rad52 associates with DNA-bound RPA and contributes to the recombination mediator activity. Accordingly, expression of a protein species that harbors the middle and C-terminal regions of Rad52 in the rad52 327 background enhances the association of Rad51 protein with a HO-made DNA double-strand break and partially complements the methylmethane sulfonate sensitivity of the mutant cells. Our results provide a mechanistic framework for rationalizing the multi-faceted role of Rad52 in recombination and DNA repair.

Received for publication, January 29, 2008

^* This work was supported by National Institutes of Health Grants P01CA92584, RO1ES07061, and RO1GM57814; Wellcome Trust Grant GR076476; Ministry of Education Youth and Sport of the Czech Republic Grants MSM 0021622413, ME 888, and MSMT LC06030; and funds from the Danish Research Council for Technology and Production Sciences and the Hartmann Foundation. 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 Figs. S1–S4.

¹ These authors contributed equally to this work.

² Present address: Dept. of Genetics and Biochemistry, Clemson University, Clemson, SC 29634.

³ Present address: Dept. of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322.

⁴ To whom correspondence should be addressed: National Center for Biomolecular Research, Masaryk University, Kamenice 5/A4, Brno 62500, Czech Republic. Tel.: 420-549493767; Fax: 420-549492556; E-mail: lkrejci{at}chemi.muni.cz.

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