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  • Title: DNA replication stress differentially regulates G1/S genes via Rad53-dependent inactivation of Nrm1.
    Author: Travesa A, Kuo D, de Bruin RA, Kalashnikova TI, Guaderrama M, Thai K, Aslanian A, Smolka MB, Yates JR, Ideker T, Wittenberg C.
    Journal: EMBO J; 2012 Apr 04; 31(7):1811-22. PubMed ID: 22333915.
    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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