The Cdk1 and Ime2 protein kinases trigger exit from meiotic prophase in Saccharomyces cerevisiae by inhibiting the Sum1 transcriptional repressor.
The induction of middle meiotic promoters is a key regulatory event in the life cycle of Saccharomyces cerevisiae that controls exit from prophase, meiosis, and spore formation. The Sum1 repressor and Ndt80 activator proteins control middle promoters by binding to overlapping DNA elements. NDT80 is controlled by a tightly regulated middle meiotic promoter through a positive autoregulatory loop and is repressed in vegetative cells by Sum1. It has previously been shown that the meiosis-specific kinase Ime2 promotes the removal of Sum1 from DNA. Here, we show that Sum1 is also regulated by the cyclin-dependent kinase, Cdk1. While sum1 phosphosite mutants that are insensitive to Cdk1 or Ime2 complete meiosis and form spores, a mutant that is insensitive to both Ime2 and Cdk1 (sum1-ci) blocks meiotic development in prophase with an ndt80Delta-like phenotype. Ectopic expression of NDT80 or mutation of a Sum1-binding element in the NDT80 promoter bypasses the sum1-ci block. Hst1 is a NAD(+)-dependent histone deacetylase that is linked to Sum1 by the Rfm1 tethering factor. Deletion of HST1 or RFM1 also bypasses the sum1-ci block. These results demonstrate that Sum1 functions as a key meiotic brake through the NDT80 promoter and that Cdk1 and Ime2 trigger exit from meiotic prophase by inhibiting the Sum1 transcriptional repression complex.
Shin
Marcus E
ME
Department of Biochemistry and Molecular Biology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA.
Skokotas
Aikaterini
A
Winter
Edward
E
D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017489:CDC28 Protein Kinase, S cerevisiae / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D049469:Meiotic Prophase I / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013172:Spores, Fungal / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C097071:NDT80 protein, S cerevisiae; D009687:Nuclear Proteins; D012097:Repressor Proteins; C100925:SUM1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D004958:Estradiol; C064979:IME2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D017489:CDC28 Protein Kinase, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; C443670:Smk1 protein, S cerevisiae
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