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


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.

SUBMITTER: Travesa A 

PROVIDER: S-EPMC3321207 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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

Travesa Anna A   Kuo Dwight D   de Bruin Robertus A M RA   Kalashnikova Tatyana I TI   Guaderrama Marisela M   Thai Kevin K   Aslanian Aaron A   Smolka Marcus B MB   Yates John R JR   Ideker Trey T   Wittenberg Curt C  

The EMBO journal 20120214 7


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  ...[more]

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