Cut5 Is Required for the Binding of Atr and DNA Polymerase α to Genotoxin-damaged Chromatin

Edgardo R. Parrilla-Castellar, Larry M. Karnitz

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

DNA damage triggers the assembly of checkpoint signaling proteins on chromatin that activate the Chk1 signaling pathway and block S-phase progression. Here we show that genotoxin-induced Chk1 activation requires Cut5 (Mus101/TopBP1) in a process that is independent of the role of Cut5 in DNA replication. Analysis of the role of Cut5 in checkpoint activation revealed that it associated with chromatin following DNA damage in a process that required RPA. Additionally, Cut5 was required for the recruitment of Atr, DNA polymerase α, and Rad1 but not RPA to chromatin following DNA damage. Taken together, these results demonstrate that Cut5 plays an integral role in the recruitment and assembly of the Chk1 signaling cascade components following DNA damage.

Original languageEnglish (US)
Pages (from-to)45507-45511
Number of pages5
JournalJournal of Biological Chemistry
Volume278
Issue number46
DOIs
StatePublished - Nov 14 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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