Choreography of the DNA damage response: Spatiotemporal relationships among checkpoint and repair proteins

Michael Lisby, Jacqueline Barlow, Rebecca C. Burgess, Rodney Rothstein

Research output: Contribution to journalArticle

660 Scopus citations

Abstract

DNA repair is an essential process for preserving genome integrity in all organisms. In eukaryotes, recombinational repair is choreographed by multiprotein complexes that are organized into centers (foci). Here, we analyze the cellular response to DNA double-strand breaks (DSBs) and replication stress in Saccharomyces cerevisiae. The Mre11 nuclease and the ATM-related Tel1 kinase are the first proteins detected at DSBs. Next, the Rfa1 single-strand DNA binding protein relocalizes to the break and recruits other key checkpoint proteins. Later and only in S and G2 phase, the homologous recombination machinery assembles at the site. Unlike the response to DSBs, Mre11 and recombination proteins are not recruited to hydroxyurea-stalled replication forks unless the forks collapse. The cellular response to DSBs and DNA replication stress is likely directed by the Mre11 complex detecting and processing DNA ends in conjunction with Sae2 and by RP-A recognizing single-stranded DNA and recruiting additional checkpoint and repair proteins.

Original languageEnglish (US)
Pages (from-to)699-713
Number of pages15
JournalCell
Volume118
Issue number6
DOIs
StatePublished - Sep 17 2004
Externally publishedYes

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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