DNA replication stress differentially regulates G1/S genes via Rad53-dependent inactivation of Nrm1
| Autor: | Travesa, Anna, Kuo, Dwight, de Bruin, Robertus A M, Kalashnikova, Tatyana I, Guaderrama, Marisela, Thai, Kevin, Aslanian, Aaron, Smolka, Marcus B, Yates, John R, Ideker, Trey, Wittenberg, Curt |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
DNA Replication
Saccharomyces cerevisiae Proteins G1 Phase Cell Cycle Proteins Saccharomyces cerevisiae Protein Serine-Threonine Kinases Methyl Methanesulfonate environment and public health Article S Phase Repressor Proteins enzymes and coenzymes (carbohydrates) Checkpoint Kinase 2 Gene Expression Regulation Fungal Hydroxyurea Camptothecin biological phenomena cell phenomena and immunity Promoter Regions Genetic DNA Damage Mutagens Transcription Factors |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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