Skip Navigation


Nucleic Acids Research Advance Access originally published online on June 19, 2008
Nucleic Acids Research 2008 36(12):4181-4190; doi:10.1093/nar/gkn362
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (3510K) Freely available
Right arrow Screen PDF (569K) Freely available
Right arrowOA All Versions of this Article:
36/12/4181    most recent
gkn362v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Hikiba, J.
Right arrow Articles by Kurumizaka, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hikiba, J.
Right arrow Articles by Kurumizaka, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2008, Vol. 36, No. 12 4181-4190
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Structural and functional analyses of the DMC1-M200V polymorphism found in the human population

Juri Hikiba1, Kouji Hirota2,3, Wataru Kagawa4, Shukuko Ikawa3, Takashi Kinebuchi4, Isao Sakane5, Yoshimasa Takizawa1, Shigeyuki Yokoyama4,6, Béatrice Mandon-Pépin7, Alain Nicolas8, Takehiko Shibata3, Kunihiro Ohta2,3 and Hitoshi Kurumizaka1,4,5,*

1Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, 2Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, 3RIKEN Advanced Research Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, 4RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama-shi, Kanagawa 230-0045, 5Institute for Biomedical Engineering, Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, 6Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, 7INRA, UMR1198; ENVA; CNRS; FRE 2857, Biologie du Developpement et Reproduction, Jouy-en-Josas, F-78350 and 8Institut Curie, Centre de Recherche, UMR7147- Centre National de la Recherche Scientifique, Université Pierre et Marie Curie, 26 rue d’Ulm, 75248 Paris Cedex 05, France

*To whom correspondence should be addressed. Tel: +81 3 5369 7315; Fax: +81 3 5367 2820; Email: kurumizaka{at}waseda.jp

Correspondence may also be addressed to Kunihiro Ohta. Tel: +81 3 5464 8834; Fax: +81 3 5464 8834; Email: kohta{at}bio.c.u-tokyo.ac.jp

Received April 18, 2008. Revised May 18, 2008. Accepted May 21, 2008.

The M200V polymorphism of the human DMC1 protein, which is an essential, meiosis-specific DNA recombinase, was found in an infertile patient, raising the question of whether this homozygous human DMC1-M200V polymorphism may cause infertility by affecting the function of the human DMC1 protein. In the present study, we determined the crystal structure of the human DMC1-M200V variant in the octameric-ring form. Biochemical analyses revealed that the human DMC1-M200V variant had reduced stability, and was moderately defective in catalyzing in vitro recombination reactions. The corresponding M194V mutation introduced in the Schizosaccharomyces pombe dmc1 gene caused a significant decrease in the meiotic homologous recombination frequency. Together, these structural, biochemical and genetic results provide extensive evidence that the human DMC1-M200V mutation impairs its function, supporting the previous interpretation that this single-nucleotide polymorphism is a source of human infertility.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
T. Ishida, Y. Takizawa, T. Kainuma, J. Inoue, T. Mikawa, T. Shibata, H. Suzuki, S. Tashiro, and H. Kurumizaka
DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange
Nucleic Acids Res., June 1, 2009; 37(10): 3367 - 3376.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.