title: Yeast IME2 functions early in meiosis upstream of cell cycle-regulated SBF and MBF targets.
abstract: BACKGROUND
  In Saccharomyces cerevisiae, the G1 cyclin/cyclin-dependent kinase (CDK) complexes Cln1,-2,-3/Cdk1 promote S phase entry during the mitotic cell cycle but do not function during meiosis. It has been proposed that the meiosis-specific protein kinase Ime2, which is required for normal timing of pre-meiotic DNA replication, is equivalent to Cln1,-2/Cdk1. These two CDK complexes directly catalyze phosphorylation of the B-type cyclin/CDK inhibitor Sic1 during the cell cycle to enable its destruction. As a result, Clb5,-6/Cdk1 become activated and facilitate initiation of DNA replication. While Ime2 is required for Sic1 destruction during meiosis, evidence now suggests that Ime2 does not directly catalyze Sic1 phosphorylation to target it for destabilization as Cln1,-2/Cdk1 do during the cell cycle.
  
  
  RESULTS
  We demonstrated that Sic1 is eventually degraded in meiotic cells lacking the IME2 gene (ime2Δ), supporting an indirect role of Ime2 in Sic1 destruction. We further examined global RNA expression comparing wild type and ime2Δ cells. Analysis of these expression data has provided evidence that Ime2 is required early in meiosis for normal transcription of many genes that are also periodically expressed during late G1 of the cell cycle.
  
  
  CONCLUSIONS
  Our results place Ime2 at a position in the early meiotic pathway that lies upstream of the position occupied by Cln1,-2/Cdk1 in the analogous cell cycle pathway. Thus, Ime2 may functionally resemble Cln3/Cdk1 in promoting S phase entry, or it could play a role even further upstream in the corresponding meiotic cascade.
authors.affiliation: Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, United States of America. brushg@karmanos.org
authors.forename: George S
authors.initials: GS
authors.lastname: Brush
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Najor
authors.forename: Alan A
authors.initials: AA
authors.lastname: Dombkowski
authors.forename: Daniela
authors.initials: D
authors.lastname: Cukovic
authors.forename: Kara E
authors.initials: KE
authors.lastname: Sawarynski
mesh_terms: D020816:Amino Acid Motifs; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002384:Catalysis; D002453:Cell Cycle; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D004261:DNA Replication; D004843:Epistasis, Genetic; D020869:Gene Expression Profiling; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008540:Meiosis; D008954:Models, Biological; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011003:Ploidies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C082719:CLN1 protein, S cerevisiae; C082721:CLN2 protein, S cerevisiae; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C508130:Whi5 protein, S cerevisiae; C064979:IME2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases