Regulation of Rad51 function by c-Abl in response to DNA damage

The RAD51 protein, a homolog of Bacterial RecA, functions in DNA double-strand break repair and genetic recombination. Whereas RAD51 catalyzes ATP-dependent pairing and strand exchange between homologous DNA molecules, regulation of this function is unknown. The c-Abl tyrosine kinase is activated by ionizing radiation and certain Other DNA-damaging agents. Here we demonstrate that c-Abl interacts constitutively with RAD51. We show that c-Abl phosphorylates RAD51 on Tyr-54 in vitro. The results also show that treatment of cells with ionizing radiation induces c-Abl-dependent phosphorylation of RAD51. Phosphorylation of RAD51 by c-Abl inhibits the binding of RAD51 to DNA and the function of RAD51 in ATP-dependent DNA strand exchange reactions. These findings represent the first demonstration that RAD51 is regulated by phosphorylation and support a functional role for c-Abl in regulating Rad51-dependent recombination in the response to DNA damage.