DNA replication stress differentially regulates G1/S genes via Rad53-dependent inactivation of Nrm1.
EMBO J
; 31(7): 1811-22, 2012 Apr 04.
Article
en En
| MEDLINE
| ID: mdl-22333915
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
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Saccharomyces cerevisiae
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Daño del ADN
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Regulación Fúngica de la Expresión Génica
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Fase G1
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Fase S
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Proteínas Serina-Treonina Quinasas
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Proteínas de Ciclo Celular
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Proteínas de Saccharomyces cerevisiae
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Replicación del ADN
Idioma:
En
Revista:
EMBO J
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos