Cut5 is required for the binding of Atr and DNA polymerase alpha to genotoxin-damaged chromatin.


Journal Article

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 alpha, 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.

Full Text

Duke Authors

Cited Authors

  • Parrilla-Castellar, ER; Karnitz, LM

Published Date

  • November 14, 2003

Published In

Volume / Issue

  • 278 / 46

Start / End Page

  • 45507 - 45511

PubMed ID

  • 14525986

Pubmed Central ID

  • 14525986

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.C300418200


  • eng

Conference Location

  • United States