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PMID: 16916637 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Molecular cell ·Vol. 23 ·No. 4 ·2006-08-00 ·Pages 483-96

de Bruin RA, Kalashnikova TI, Chahwan C, McDonald WH, Wohlschlegel J, Yates J, Russell P, Wittenberg C

Abstract

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
Amino Acid Sequence Cell Cycle Proteins/metabolism Checkpoint Kinase 2 Feedback, Physiological G1 Phase Gene Expression Regulation, Fungal Genes, Fungal/genetics Hydroxyurea/pharmacology Intracellular Signaling Peptides and Proteins Models, Genetic Molecular Sequence Data Mutation/genetics Promoter Regions, Genetic/genetics Protein Binding Protein Serine-Threonine Kinases/metabolism RNA, Messenger/genetics,metabolism Repressor Proteins/chemistry,metabolism Saccharomyces cerevisiae/cytology,drug effects Saccharomyces cerevisiae Proteins/chemistry,metabolism Schizosaccharomyces/metabolism Trans-Activators/metabolism Transcription Factors/metabolism Transcription, Genetic/drug effects
Chemicals
Cell Cycle Proteins Intracellular Signaling Peptides and Proteins MBF1 protein, S cerevisiae Nrm1 protein, S cerevisiae RNA, Messenger Repressor Proteins SBF protein, S cerevisiae Saccharomyces cerevisiae Proteins Trans-Activators Transcription Factors Checkpoint Kinase 2 MEC1 protein, S cerevisiae Protein Serine-Threonine Kinases RAD53 protein, S cerevisiae Hydroxyurea
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
de Bruin Robertus A M
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Kalashnikova Tatyana I
Chahwan Charly
McDonald W Hayes
Wohlschlegel James
Yates John
Russell Paul
Wittenberg Curt
Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-2765
Published
2006-08-00
Pages
483-96
Language
English
Region
United States
NLM ID
9802571
Subset
IM
Grants
NCI NIH HHS · CA77325 · United States
NIGMS NIH HHS · GM059441 · United States
NIGMS NIH HHS · GM59447 · United States
NCRR NIH HHS · P4 1RR11823 · United States
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