Regulation of Rad51 function by phosphorylation.

Abstract:: Rad51 is a key enzyme involved in DNA double-strand break repair by homologous recombination. Here, we show that in response to DNA damage, budding yeast Rad51 is phosphorylated on Ser 192 in a manner that is primarily mediated by the DNA-damage-responsive protein kinase Mec1. We show that mutating Rad51 Ser 192 to Ala or Glu confers hypersensitivity to DNA damage and homologous-recombination defects. Furthermore, biochemical analyses indicate that Ser 192 is required for Rad51 adenosine triphosphate hydrolysis and DNA-binding activity in vitro, whereas mutation of Ser 192 does not interfere with Rad51 multimer formation. These data suggest a model in which Mec1-mediated phosphorylation of Rad51 Ser 192 in response to DNA damage controls Rad51 activity and DNA repair by homologous recombination.

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