Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl

Cells from individuals with the recessive cancer-prone disorder ataxia tela ngiectasia (A-T) are hypersensitive to ionizing radiation (I-R). ATM (mutat ed 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 f ollowing I-R. Rad51 is a homologue of bacterial RecA protein required for D NA recombination and repair. Here we demonstrate that there is an I-R-induc ed 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 R ad51 in vitro and in vivo. In assays using purified components, phosphoryla tion of Rad51 by c-Abl enhances complex formation between Rad51 and Rad52, which cooperates with Rad51 in recombination and repair. After I-R, an incr ease in association between Rad51 and Rad52 occurs in wild-type cells but n ot in cells with mutations that compromise ATM or c-Abl. Our data suggest s ignaling mediated through ATM, and c-Abl is required for the correct posttr anslational modification of Rad51, which is critical for the assembly of Ra d51 repair protein complex following I-R.