Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl - PubMed (original) (raw)
. 1999 Apr 30;274(18):12748-52.
doi: 10.1074/jbc.274.18.12748.
S S Yuan, W Liu, Y Xu, K Trujillo, B Song, F Cong, S P Goff, Y Wu, R Arlinghaus, D Baltimore, P J Gasser, M S Park, P Sung, E Y Lee
Affiliations
- PMID: 10212258
- DOI: 10.1074/jbc.274.18.12748
Free article
Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl
G Chen et al. J Biol Chem. 1999.
Free article
Abstract
Cells from individuals with the recessive cancer-prone disorder ataxia telangiectasia (A-T) are hypersensitive to ionizing radiation (I-R). ATM (mutated in A-T) is a protein kinase whose activity is stimulated by I-R. c-Abl, a nonreceptor tyrosine kinase, interacts with ATM and is activated by ATM following I-R. Rad51 is a homologue of bacterial RecA protein required for DNA recombination and repair. Here we demonstrate that there is an I-R-induced Rad51 tyrosine phosphorylation, and this induction is dependent on both ATM and c-Abl. ATM, c-Abl, and Rad51 can be co-immunoprecipitated from cell extracts. Consistent with the physical interaction, c-Abl phosphorylates Rad51 in vitro and in vivo. In assays using purified components, phosphorylation of Rad51 by c-Abl enhances complex formation between Rad51 and Rad52, which cooperates with Rad51 in recombination and repair. After I-R, an increase in association between Rad51 and Rad52 occurs in wild-type cells but not in cells with mutations that compromise ATM or c-Abl. Our data suggest signaling mediated through ATM, and c-Abl is required for the correct post-translational modification of Rad51, which is critical for the assembly of Rad51 repair protein complex following I-R.
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