SPELL - S. cerevisiae

Citation	Travesa A, Kuo D, de Bruin RA, Kalashnikova TI, Guaderrama M, Thai K, Aslanian A, Smolka MB, Yates JR 3rd, Ideker T, Wittenberg C. DNA replication stress differentially regulates G1/S genes via Rad53-dependent inactivation of Nrm1. The EMBO journal, 2012.
PubMed ID	22333915
Short Description	DNA replication stress differentially regulates G1/S genes via Rad53-dependent inactivation of Nrm1.
# of Conditions	61
Full Description	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.
Tags	cell cycle regulation, DNA damage stimulus, stress