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

  作者 Travesa, A; Kuo, D; de Bruin, RAM; Kalashnikova, TI; Guaderrama, M; Thai, K; Aslanian, A; Smolka, MB; Yates, JR; Ideker, T; Wittenberg, C  
  选自 期刊  EMBO journal;  卷期  2012年31-7;  页码  1811-1822  
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[摘要]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. The EMBO Journal (2012) 31, 1811-1822. doi: 10.1038/emboj.2012.28; Published online 14 February 2012

 
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