title: Constraining G1-specific transcription to late G1 phase: the MBF-associated corepressor Nrm1 acts via negative feedback.
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.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Robertus A M
authors.initials: RA
authors.lastname: de Bruin
authors.forename: Tatyana I
authors.initials: TI
authors.lastname: Kalashnikova
authors.forename: Charly
authors.initials: C
authors.lastname: Chahwan
authors.forename: W Hayes
authors.initials: WH
authors.lastname: McDonald
authors.forename: James
authors.initials: J
authors.lastname: Wohlschlegel
authors.forename: John
authors.initials: J
authors.lastname: Yates
authors.forename: Paul
authors.initials: P
authors.lastname: Russell
authors.forename: Curt
authors.initials: C
authors.lastname: Wittenberg
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2; D025461:Feedback, Physiological; D016193:G1 Phase; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics; D006918:Hydroxyurea / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; C106951:MBF1 protein, S cerevisiae; C513403:Nrm1 protein, S cerevisiae; D012333:RNA, Messenger; D012097:Repressor Proteins; C081540:SBF protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D064447:Checkpoint Kinase 2; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D006918:Hydroxyurea