Biochemical analysis of the human DMC1-I37N polymorphism

Juri Hikiba, Yoshimasa Takizawa, Shukuko Ikawa, Takehiko Shibata, Hitoshi Kurumizaka

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    The DMC1 protein, a meiosis-specific DNA recombinase, promotes homologous pairing and strand exchange. The I37N single nucleotide polymorphism of the human DMC1 protein was reported as a result of human genome sequencing projects. In this study, we purified the human DMC1-I37N variant, as a recombinant protein. The DMC1 protein is known to require DNA for efficient ATP hydrolysis. By contrast, the DMC1-I37N variant efficiently hydrolyzed ATP in the absence of DNA. Like the conventional DMC1 protein, the DMC1-I37N variant promoted strand exchange, but it required a high Ca2+ concentration (4-8 mm), a condition that inactivates the strand-exchange activity of the conventional DMC1 protein. These biochemical differences between the DMC1 and DMC1-I37N proteins suggest that the DMC1-I37N polymorphism may be a source of improper meiotic recombination, causing meiotic defects in humans.

    Original languageEnglish
    Pages (from-to)457-465
    Number of pages9
    JournalFEBS Journal
    Volume276
    Issue number2
    DOIs
    Publication statusPublished - 2009 Jan

    Fingerprint

    Polymorphism
    Proteins
    DNA
    Adenosine Triphosphate
    Human Genome Project
    Recombinases
    Meiosis
    Recombinant Proteins
    Genetic Recombination
    Single Nucleotide Polymorphism
    Hydrolysis
    Nucleotides
    Genes
    Defects

    Keywords

    • DMC1
    • DMC1-I37N
    • Homologous recombination
    • Meiosis
    • SNP

    ASJC Scopus subject areas

    • Biochemistry
    • Cell Biology
    • Molecular Biology

    Cite this

    Hikiba, J., Takizawa, Y., Ikawa, S., Shibata, T., & Kurumizaka, H. (2009). Biochemical analysis of the human DMC1-I37N polymorphism. FEBS Journal, 276(2), 457-465. https://doi.org/10.1111/j.1742-4658.2008.06786.x

    Biochemical analysis of the human DMC1-I37N polymorphism. / Hikiba, Juri; Takizawa, Yoshimasa; Ikawa, Shukuko; Shibata, Takehiko; Kurumizaka, Hitoshi.

    In: FEBS Journal, Vol. 276, No. 2, 01.2009, p. 457-465.

    Research output: Contribution to journalArticle

    Hikiba, J, Takizawa, Y, Ikawa, S, Shibata, T & Kurumizaka, H 2009, 'Biochemical analysis of the human DMC1-I37N polymorphism', FEBS Journal, vol. 276, no. 2, pp. 457-465. https://doi.org/10.1111/j.1742-4658.2008.06786.x
    Hikiba J, Takizawa Y, Ikawa S, Shibata T, Kurumizaka H. Biochemical analysis of the human DMC1-I37N polymorphism. FEBS Journal. 2009 Jan;276(2):457-465. https://doi.org/10.1111/j.1742-4658.2008.06786.x
    Hikiba, Juri ; Takizawa, Yoshimasa ; Ikawa, Shukuko ; Shibata, Takehiko ; Kurumizaka, Hitoshi. / Biochemical analysis of the human DMC1-I37N polymorphism. In: FEBS Journal. 2009 ; Vol. 276, No. 2. pp. 457-465.
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