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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Camptothecin / pharmacology
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Checkpoint Kinase 2
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DNA Damage / genetics*
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DNA Replication*
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G1 Phase / genetics*
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Gene Expression Regulation, Fungal*
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Hydroxyurea / pharmacology
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Methyl Methanesulfonate / pharmacology
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Mutagens / pharmacology
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Promoter Regions, Genetic
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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S Phase / genetics*
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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Cell Cycle Proteins
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Mutagens
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Nrm1 protein, S cerevisiae
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Methyl Methanesulfonate
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Checkpoint Kinase 2
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Protein Serine-Threonine Kinases
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RAD53 protein, S cerevisiae
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Hydroxyurea
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Camptothecin