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

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.
Mesh Terms:
Cell Cycle Proteins, DNA-Binding Proteins, Phosphorylation, Protein Binding, Protein Kinases, Protein Processing, Post-Translational, Protein-Serine-Threonine Kinases, Proteins, Proto-Oncogene Proteins c-abl, Rad51 Recombinase, Rad52 DNA Repair and Recombination Protein, Recombination, Genetic, Saccharomyces cerevisiae Proteins, Tumor Suppressor Proteins, Tyrosine
J. Biol. Chem.
Date: Apr. 30, 1999
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