Reference: Travesa A, et al. (2012) DNA replication stress differentially regulates G1/S genes via Rad53-dependent inactivation of Nrm1. EMBO J 31(7):1811-22

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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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Journal Article | Research Support, N.I.H., Extramural
Authors
Travesa A, Kuo D, de Bruin RA, Kalashnikova TI, Guaderrama M, Thai K, Aslanian A, Smolka MB, Yates JR 3rd, Ideker T, ... Show all
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