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

J Biol Chem. 1998 Feb 13;273(7):3799-802. doi: 10.1074/jbc.273.7.3799.

Abstract

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.

MeSH terms

  • Cell Line
  • DNA Damage / radiation effects*
  • DNA Repair / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation / genetics
  • Immunoblotting
  • Phosphorylation
  • Phosphotyrosine / analysis
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Rad51 Recombinase
  • Radiation, Ionizing
  • Recombination, Genetic / genetics

Substances

  • DNA-Binding Proteins
  • Phosphotyrosine
  • Proto-Oncogene Proteins c-abl
  • Rad51 Recombinase