c-ABL tyrosine kinase stabilizes RAD51 chromatin association

Hiroko Shimizu, Milena Popova, Fabrice Fleury, Masahiko Kobayashi, Naoyuki Hayashi, Isao Sakane, Hitoshi Kurumizaka, Ashok R. Venkitaraman, Masayuki Takahashi, Ken ichi Yamamoto*

*この研究の対応する著者

    研究成果: Article査読

    23 被引用数 (Scopus)

    抄録

    The assembly of RAD51 recombinase on DNA substrates at sites of breakage is essential for their repair by homologous recombination repair (HRR). The signaling pathway that triggers RAD51 assembly at damage sites to form subnuclear foci is unclear. Here, we provide evidence that c-ABL, a tyrosine kinase activated by DNA damage which phosphorylates RAD51 on Tyr-315, works at a previously unrecognized, proximal step to initiate RAD51 assembly. We first show that c-ABL associates with chromatin after DNA damage in a manner dependent on its kinase activity. Using RAD51 mutants that are unable to oligomerize to form a nucleoprotein filament, we separate RAD51 assembly on DNA to form foci into two steps: stable chromatin association followed by oligomerization. We show that phosphorylation on Tyr-315 by c-ABL is required for chromatin association of oligomerization-defective RAD51 mutants, but is insufficient to restore oligomerization. Our findings suggest a new model for the regulation of early steps of HRR.

    本文言語English
    ページ(範囲)286-291
    ページ数6
    ジャーナルBiochemical and Biophysical Research Communications
    382
    2
    DOI
    出版ステータスPublished - 2009 5 1

    ASJC Scopus subject areas

    • 生化学
    • 生物理学
    • 細胞生物学
    • 分子生物学

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