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

J. Biol. Chem., Vol. 280, Issue 29, 26886-26895, July 22, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/29/26886    most recent M502248200v1 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 Bugreev, D. V. Articles by Mazin, A. V. Search for Related Content PubMed PubMed Citation Articles by Bugreev, D. V. Articles by Mazin, A. V. Social Bookmarking                      What's this?

Activation of Human Meiosis-specific Recombinase Dmc1 by Ca^2+*

Dmitry V. Bugreev, Efim I. Golub¶, Alicja Z. Stasiak||, Andrzej Stasiak||, and Alexander V. Mazin**

From the Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, the Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia, the ^¶Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, and the ^||Laboratoire d'Analyse Ultrastructurale, Université de Lausanne, CH-1015 Lausanne-Dorigny, Switzerland

Rad51 and its meiotic homolog Dmc1 are key proteins of homologous recombination in eukaryotes. These proteins form nucleoprotein complexes on single-stranded DNA that promote a search for homology and that perform DNA strand exchange, the two essential steps of genetic recombination. Previously, we demonstrated that Ca²⁺ greatly stimulates the DNA strand exchange activity of human (h) Rad51 protein (Bugreev, D. V., and Mazin, A. V. (2004) Proc. Natl. Acad. Sci. U. S. A. 101, 9988–9993). Here, we show that the DNA strand exchange activity of hDmc1 protein is also stimulated by Ca²⁺. However, the mechanism of stimulation of hDmc1 protein appears to be different from that of hRad51 protein. In the case of hRad51 protein, Ca²⁺ acts primarily by inhibiting its ATPase activity, thereby preventing self-conversion into an inactive ADP-bound complex. In contrast, we demonstrate that hDmc1 protein does not self-convert into a stable ADP-bound complex. The results indicate that activation of hDmc1 is mediated through conformational changes induced by free Ca²⁺ ion binding to a protein site that is distinct from the Mg²⁺·ATP-binding center. These conformational changes are manifested by formation of more stable filamentous hDmc1·single-stranded DNA complexes. Our results demonstrate a universal role of Ca²⁺ in stimulation of mammalian DNA strand exchange proteins and reveal diversity in the mechanisms of this stimulation.

Received for publication, February 28, 2005 , and in revised form, May 9, 2005.

^* This work was supported by the Drexel University Synergy Award, National Institutes of Health Grant CA100839 (to A. V. M.), and Swiss National Foundation Grant 3100A0-103962 (to A. S.). 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.

^** To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, MS 497, NCB, Rm. 10103, Drexel University College of Medicine, 245 N. 15th St., Philadelphia, PA 19102-1192. Tel.: 215-762-7195; Fax: 215-762-4452; E-mail: avm28{at}drexel.edu.

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

This article has been cited by other articles:

				T. B. Usdin, M. Paciga, T. Riordan, J. Kuo, A. Parmelee, G. Petukova, R. D. Camerini-Otero, and E. Mezey Tuberoinfundibular Peptide of 39 Residues Is Required for Germ Cell Development Endocrinology, September 1, 2008; 149(9): 4292 - 4300. [Abstract] [Full Text] [PDF]

				I. Sakane, C. Kamataki, Y. Takizawa, M. Nakashima, S. Toki, H. Ichikawa, S. Ikawa, T. Shibata, and H. Kurumizaka Filament formation and robust strand exchange activities of the rice DMC1A and DMC1B proteins Nucleic Acids Res., August 1, 2008; 36(13): 4266 - 4276. [Abstract] [Full Text] [PDF]

				S. D. Sheridan, X. Yu, R. Roth, J. E. Heuser, M. G. Sehorn, P. Sung, E. H. Egelman, and D. K. Bishop A comparative analysis of Dmc1 and Rad51 nucleoprotein filaments Nucleic Acids Res., July 1, 2008; 36(12): 4057 - 4066. [Abstract] [Full Text] [PDF]

				J. Hikiba, K. Hirota, W. Kagawa, S. Ikawa, T. Kinebuchi, I. Sakane, Y. Takizawa, S. Yokoyama, B. Mandon-Pepin, A. Nicolas, et al. Structural and functional analyses of the DMC1-M200V polymorphism found in the human population Nucleic Acids Res., July 1, 2008; 36(12): 4181 - 4190. [Abstract] [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]

				R. J. Pezza, O. N. Voloshin, F. Vanevski, and R. D. Camerini-Otero Hop2/Mnd1 acts on two critical steps in Dmc1-promoted homologous pairing Genes & Dev., July 15, 2007; 21(14): 1758 - 1766. [Abstract] [Full Text] [PDF]

				M. Ploquin, G. V. Petukhova, D. Morneau, U. Dery, A. Bransi, A. Stasiak, R. D. Camerini-Otero, and J.-Y. Masson Stimulation of fission yeast and mouse Hop2-Mnd1 of the Dmc1 and Rad51 recombinases Nucleic Acids Res., April 10, 2007; (2007) gkm174v1. [Abstract] [Full Text] [PDF]

				L.-T. Chen, T.-P. Ko, Y.-C. Chang, K.-A. Lin, C.-S. Chang, A. H.-J. Wang, and T.-F. Wang Crystal structure of the left-handed archaeal RadA helical filament: identification of a functional motif for controlling quaternary structures and enzymatic functions of RecA family proteins Nucleic Acids Res., March 19, 2007; 35(6): 1787 - 1801. [Abstract] [Full Text] [PDF]

				X. Qian, Y. He, X. Ma, M. N. Fodje, P. Grochulski, and Y. Luo Calcium Stiffens Archaeal Rad51 Recombinase from Methanococcus voltae for Homologous Recombination J. Biol. Chem., December 22, 2006; 281(51): 39380 - 39387. [Abstract] [Full Text] [PDF]

				T. M. Holzen, P. P. Shah, H. A. Olivares, and D. K. Bishop Tid1/Rdh54 promotes dissociation of Dmc1 from nonrecombinogenic sites on meiotic chromatin Genes & Dev., September 15, 2006; 20(18): 2593 - 2604. [Full Text] [PDF]

				N. Sarai, W. Kagawa, T. Kinebuchi, A. Kagawa, K. Tanaka, K. Miyagawa, S. Ikawa, T. Shibata, H. Kurumizaka, and S. Yokoyama Stimulation of Dmc1-mediated DNA strand exchange by the human Rad54B protein Nucleic Acids Res., September 11, 2006; 34(16): 4429 - 4437. [Abstract] [Full Text] [PDF]

				M. K. K. Shivji, O. R. Davies, J. M. Savill, D. L. Bates, L. Pellegrini, and A. R. Venkitaraman A region of human BRCA2 containing multiple BRC repeats promotes RAD51-mediated strand exchange Nucleic Acids Res., September 1, 2006; 34(14): 4000 - 4011. [Abstract] [Full Text] [PDF]

				S. Sheridan and D. K. Bishop Red-Hed regulation: recombinase Rad51, though capable of playing the leading role, may be relegated to supporting Dmc1 in budding yeast meiosis. Genes & Dev., July 1, 2006; 20(13): 1685 - 1691. [Full Text] [PDF]

				M.-H. Lee, Y.-C. Chang, E. L. Hong, J. Grubb, C.-S. Chang, D. K. Bishop, and T.-F. Wang Calcium Ion Promotes Yeast Dmc1 Activity via Formation of Long and Fine Helical Filaments with Single-stranded DNA J. Biol. Chem., December 9, 2005; 280(49): 40980 - 40984. [Abstract] [Full Text] [PDF]