title: Phosphorylation of the MBF repressor Yox1p by the DNA replication checkpoint keeps the G1/S cell-cycle transcriptional program active.
abstract: BACKGROUND
  In fission yeast Schizosaccharomyces pombe G1/S cell-cycle regulated transcription depends upon MBF. A negative feedback loop involving Nrm1p and Yox1p bound to MBF leads to transcriptional repression as cells exit G1 phase. However, activation of the DNA replication checkpoint response during S phase results in persistent expression of MBF-dependent genes.
  
  
  RESULTS
  This report shows that Yox1p binding to MBF is Nrm1-dependent and that Yox1p and Nrm1p require each other to bind and repress MBF targets. In response to DNA replication stress both Yox1p and Nrm1p dissociate from MBF at promoters leading to de-repression of MBF targets. Inactivation of Yox1p is an essential part of the checkpoint response. Cds1p (human Chk2p) checkpoint protein kinase-dependent phosphorylation of Yox1p promotes its dissociation from the MBF transcription factor. We establish that phosphorylation of Yox1p at Ser114, Thr115 is required for maximal checkpoint-dependent activation of the G1/S cell-cycle transcriptional program.
  
  
  CONCLUSIONS
  This study shows that checkpoint-dependent phosphorylation of Yox1p at Ser114, Thr115 results in de-repression of the MBF transcriptional program. The remodeling of the cell cycle transcriptional program by the DNA replication checkpoint is likely to comprise an important mechanism for the avoidance of genomic instability.
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom.
authors.forename: Catia
authors.initials: C
authors.lastname: Caetano
authors.forename: Steffi
authors.initials: S
authors.lastname: Klier
authors.forename: Robertus A M
authors.initials: RA
authors.lastname: de Bruin
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D004261:DNA Replication / Q000235:genetics / Q000502:physiology*; D016193:G1 Phase / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism* / Q000502:physiology; D030781:Organisms, Genetically Modified; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology; D016196:S Phase / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C489911:DSC1 protein, S pombe; D018398:Homeodomain Proteins; C531391:Nrm1 protein, S pombe; D012097:Repressor Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C545558:Yox1 protein, S pombe; D011494:Protein Kinases