Constraining G1-specific transcription to late G1 phase: the MBF-associated corepressor Nrm1 acts via negative feedback.

de Bruin RA, Kalashnikova TI, Chahwan C, McDonald WH, Wohlschlegel J, Yates J, Russell P, Wittenberg C
Mol Cell. 2006 23 (4): 483-96

PMID: 16916637 · DOI:10.1016/j.molcel.2006.06.025

G1-specific transcription in yeast depends upon SBF and MBF. We have identified Nrm1 (negative regulator of MBF targets 1), as a stable component of MBF. NRM1 (YNR009w), an MBF-regulated gene expressed during late G1 phase, associates with G1-specific promoters via MBF. Transcriptional repression upon exit from G1 phase requires both Nrm1 and MBF. Inactivation of Nrm1 results in prolonged expression of MBF-regulated transcripts and leads to hydroxyurea (HU) resistance and enhanced bypass of rad53Delta- and mec1Delta-associated lethality. Constitutive expression of a stabilized form of Nrm1 represses MBF targets and leads to HU sensitivity. The fission yeast homolog SpNrm1, encoded by the MBF target gene nrm1(+) (SPBC16A3.07c), binds to MBF target genes and acts as a corepressor. In both yeasts, MBF represses G1-specific transcription outside of G1 phase. A negative feedback loop involving Nrm1 bound to MBF leads to transcriptional repression as cells exit G1 phase.

MeSH Terms (23)

Amino Acid Sequence Cell Cycle Proteins Checkpoint Kinase 2 Feedback, Physiological G1 Phase Gene Expression Regulation, Fungal Genes, Fungal Hydroxyurea Intracellular Signaling Peptides and Proteins Models, Genetic Molecular Sequence Data Mutation Promoter Regions, Genetic Protein-Serine-Threonine Kinases Protein Binding Repressor Proteins RNA, Messenger Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Schizosaccharomyces Trans-Activators Transcription, Genetic Transcription Factors

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