ATM-dependent phosphorylation of the checkpoint clamp regulates repair pathways and maintains genomic stability

Research output: Contribution to journalArticlepeer-review

Abstract

Upon genotoxic stress and during normal S phase, ATM phosphorylates the checkpoint clamp protein Rad9 in a manner that depends on Ser272. Ser272 is the only known ATM-dependent phosphorylation site in human Rad9. However, Ser272 phosphorylation is not required for survival or checkpoint activation after DNA damage. The physiological function of Ser272 remains elusive. Here, we show that ATM-dependent Rad9Ser272 phosphorylation requires the MRN complex and controls repair pathways. Furthermore, the mutant cells accumulate large numbers of chromosome breaks and induce gross chromosomal rearrangements. Our findings establish a new and unexpected role for ATM: it phosphorylates the checkpoint clamp in order to control repair pathways, thereby maintaining genomic integrity during unperturbed cell cycle and upon DNA damage.

Original languageEnglish (US)
Pages (from-to)1796-1803
Number of pages8
JournalCell Cycle
Volume11
Issue number9
DOIs
StatePublished - May 1 2012

Keywords

  • ATM
  • Checkpoint
  • Phosphorylation
  • Rad9
  • Repair

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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