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

Juri Hikiba, Kouji Hirota, Wataru Kagawa, Shukuko Ikawa, Takashi Kinebuchi, Isao Sakane, Yoshimasa Takizawa, Shigeyuki Yokoyama, Béatrice Mandon-Pépin, Alain Nicolas, Takehiko Shibata, Kunihiro Ohta, Hitoshi Kurumizaka*

*この研究の対応する著者

    研究成果: Article査読

    24 被引用数 (Scopus)

    抄録

    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.

    本文言語English
    ページ(範囲)4181-4190
    ページ数10
    ジャーナルNucleic Acids Research
    36
    12
    DOI
    出版ステータスPublished - 2008 7

    ASJC Scopus subject areas

    • 遺伝学

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