Regulation of Rad51 function by phosphorylation

Sonja Flott1, Youngho Kwon, Ying Zhang Pigli

  • 1Department of Biochemistry, Wellcome Trust and Cancer Research UK, Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.

EMBO Reports
|July 9, 2011
PubMed

Insights

Budding yeast Rad51 phosphorylation on Ser 192 by Mec1 kinase is crucial for DNA repair. This modification regulates Rad51

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Rad51 is essential for DNA double-strand break repair via homologous recombination.
  • DNA damage response pathways regulate proteins involved in DNA repair.

Purpose of the Study:

  • To investigate the role of Rad51 phosphorylation in DNA repair.
  • To identify the kinase responsible for Rad51 phosphorylation and its functional consequences.

Main Methods:

  • Site-directed mutagenesis of Rad51 Ser 192.
  • Analysis of DNA damage sensitivity and homologous recombination.
  • In vitro biochemical assays for ATP hydrolysis and DNA binding.

Main Results:

  • Mec1 kinase mediates Rad51 phosphorylation on Ser 192 in response to DNA damage.
  • Mutations at Ser 192 cause hypersensitivity to DNA damage and impaired homologous recombination.
  • Ser 192 is critical for Rad51's ATPase activity and DNA binding in vitro, but not multimer formation.

Conclusions:

  • Mec1-mediated phosphorylation of Rad51 Ser 192 is a key regulatory mechanism for DNA repair by homologous recombination.
  • Phosphorylation at Ser 192 controls Rad51's enzymatic activity and DNA repair function.

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