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- Title
DNA replication stress differentially regulates G1/S genes via Rad53-dependent inactivation of Nrm1.
- Authors
Travesa, Anna; Kuo, Dwight; de Bruin, Robertus A M; Kalashnikova, Tatyana I; Guaderrama, Marisela; Thai, Kevin; Aslanian, Aaron; Smolka, Marcus B; Yates, John R, 3rd; Ideker, Trey; Wittenberg, Curt
- 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.
- Publication
The EMBO journal, 2012, Vol 31, Issue 7, p1811
- ISSN
1460-2075
- Publication type
Journal Article
- DOI
10.1038/emboj.2012.28