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

658 Citations (Scopus)

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

Fingerprint

DNA Damage
Repair
DNA
Multiprotein Complexes
Proteins
Hydroxyurea
Double-Stranded DNA Breaks
G2 Phase
Single-Stranded DNA
Homologous Recombination
DNA-Binding Proteins
Eukaryota
DNA Replication
S Phase
DNA Repair
Protein Kinases
Genetic Recombination
Saccharomyces cerevisiae
Automatic teller machines
Genome

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Choreography of the DNA damage response : Spatiotemporal relationships among checkpoint and repair proteins. / Lisby, Michael; Barlow, Jacqueline; Burgess, Rebecca C.; Rothstein, Rodney.

In: Cell, Vol. 118, No. 6, 17.09.2004, p. 699-713.

Research output: Contribution to journalArticle

Lisby, Michael ; Barlow, Jacqueline ; Burgess, Rebecca C. ; Rothstein, Rodney. / Choreography of the DNA damage response : Spatiotemporal relationships among checkpoint and repair proteins. In: Cell. 2004 ; Vol. 118, No. 6. pp. 699-713.
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