title: 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.
authors: Department of Biochemistry, Wellcome Trust and Cancer Research UK, Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors: Sonja
authors: S
authors: Flott
authors: Youngho
authors: Y
authors: Kwon
authors: Ying Zhang
authors: YZ
authors: Pigli
authors: Phoebe A
authors: PA
authors: Rice
authors: Patrick
authors: P
authors: Sung
authors: Stephen P
authors: SP
authors: Jackson
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006868:Hydrolysis; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051135:Rad51 Recombinase / Q000235:genetics* / Q000378:metabolism*; D011995:Recombination, Genetic / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D051135:Rad51 Recombinase; D000251:Adenosine Triphosphatases