REGULATION OF RAD51 FUNCTION BY C-ABL IN RESPONSE TO DNA-DAMAGE

The Rad51 protein, a homolog of bacterial RecA, functions in DNA doubl e-strand break repair and genetic recombination. Whereas Rad51 catalyz es ATP-dependent pairing and strand exchange between homologous DNA mo lecules, regulation of this function is unknown. The c-Abl tyrosine ki nase 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 ind uces c-Abl dependent phosphorylation of Rad51. Phosphorylation of Rad5 1 by c-Abl inhibits the binding of Rad51 to DNA and the function of Ra d51 in ATP-dependent DNA strand exchange reactions. These findings rep resent the first demonstration that Rad51 is regulated by phosphorylat ion and support a functional role for c-Abl in regulating Rad51-depend ent recombination in the response to DNA damage.