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EMBO J. 2012 Apr 4;31(7):1811-22. doi: 10.1038/emboj.2012.28. Epub 2012 Feb 14.

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

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  • 1Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA.

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.

PMID:
22333915
[PubMed - indexed for MEDLINE]
PMCID:
PMC3321207
Free PMC Article

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