1. c-ABL tyrosine kinase stabilizes RAD51 chromatin association
- Author
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Masahiko Kobayashi, Ken Ichi Yamamoto, Milena Popova, Naoyuki Hayashi, Ashok R. Venkitaraman, Masayuki Takahashi, Isao Sakane, Hitoshi Kurumizaka, Fabrice Fleury, and Hiroko Shimizu
- Subjects
DNA repair ,DNA damage ,genetic processes ,Biophysics ,RAD51 ,Biology ,Biochemistry ,c-ABL ,Cell Line ,Tyrosine phosphorylation ,chemistry.chemical_compound ,Humans ,Phosphorylation ,Kinase activity ,Proto-Oncogene Proteins c-abl ,Molecular Biology ,Cell Biology ,BRCA2 ,Molecular biology ,Chromatin ,Cell biology ,enzymes and coenzymes (carbohydrates) ,chemistry ,ATM ,Homologous recombination repair ,health occupations ,Tyrosine ,Rad51 Recombinase ,biological phenomena, cell phenomena, and immunity ,Homologous recombination ,DNA ,DNA Damage - Abstract
金沢大学がん研究所がん分子細胞制御, 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. © 2009 Elsevier Inc. All rights reserved.
- Published
- 2009
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