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

Research output: Contribution to journalArticle

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 - May 1 2009

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell 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