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

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    21 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)286-291
    Number of pages6
    JournalBiochemical and Biophysical Research Communications
    Volume382
    Issue number2
    DOIs
    Publication statusPublished - 2009 May 1

    Keywords

    • ATM
    • BRCA2
    • c-ABL
    • Homologous recombination repair
    • RAD51
    • Tyrosine phosphorylation

    ASJC Scopus subject areas

    • Biochemistry
    • Biophysics
    • Cell Biology
    • Molecular Biology

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  • Cite this

    Shimizu, H., Popova, M., Fleury, F., Kobayashi, M., Hayashi, N., Sakane, I., Kurumizaka, H., Venkitaraman, A. R., Takahashi, M., & Yamamoto, K. I. (2009). c-ABL tyrosine kinase stabilizes RAD51 chromatin association. Biochemical and Biophysical Research Communications, 382(2), 286-291. https://doi.org/10.1016/j.bbrc.2009.03.020