Rad52 recruitment is DNA replication independent and regulated by Cdc28 and the Mec1 kinase

Jacqueline Barlow, Rodney Rothstein

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Recruitment of the homologous recombination machinery to sites of double-strand breaks is a cell cycle-regulated event requiring entry into S phase and CDK1 activity. Here, we demonstrate that the central recombination protein, Rad52, forms foci independent of DNA replication, and its recruitment requires B-type cyclin/CDK1 activity. Induction of the intra-S-phase checkpoint by hydroxyurea (HU) inhibits Rad52 focus formation in response to ionizing radiation. This inhibition is dependent upon Mec1/Tel1 kinase activity, as HU-treated cells form Rad52 foci in the presence of the PI3 kinase inhibitor caffeine. These Rad52 foci colocalize with foci formed by the replication clamp PCNA. These results indicate that Mec1 activity inhibits the recruitment of Rad52 to both sites of DNA damage and stalled replication forks during the intra-S-phase checkpoint. We propose that B-type cyclins promote the recruitment of Rad52 to sites of DNA damage, whereas Mec1 inhibits spurious recombination at stalled replication forks.

Original languageEnglish (US)
Pages (from-to)1121-1130
Number of pages10
JournalEMBO Journal
Volume28
Issue number8
DOIs
StatePublished - Apr 22 2009
Externally publishedYes

Keywords

  • Checkpoints
  • DNAdamage
  • Recombination
  • Replication

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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