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DNA replication stress differentially regulates G1/S genes via Rad53-dependent inactivation of Nrm1.

Authors
  • A, Travesa
  • D, Kuo
  • Ra, De Bruin
  • Ti, Kalashnikova
  • M, Guaderrama
  • K, Thai
  • A, Aslanian
  • Mb, Smolka
  • 3rd, Yates Jr
  • Trey Ideker
  • C, Wittenberg
Type
Published Article
Journal
The EMBO Journal
Publisher
EMBO
Volume
31
Issue
7
Pages
1811–1822
Identifiers
DOI: 10.1038/emboj.2012.28
Source
Ideker Lab
License
Unknown

Abstract

MBF and SBF transcription factors regulate a large family of coordinately expressed G1/S genes required for early cell-cycle functions including DNA replication and repair. SBF is inactivated upon S-phase entry by Clb/CDK whereas MBF targets are repressed by the co-repressor, Nrm1. Using genome-wide expression analysis of cells treated with methyl methane sulfonate (MMS), hydroxyurea (HU) or camptothecin (CPT), we show that genotoxic stress during S phase specifically induces MBF-regulated genes. This occurs via direct phosphorylation of Nrm1 by Rad53, the effector checkpoint kinase, which prevents its binding to MBF target promoters. We conclude that MBF-regulated genes are distinguished from SBF-regulated genes by their sensitivity to activation by the S-phase checkpoint, thereby, providing an effective mechanism for enhancing DNA replication and repair and promoting genome stability.

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