PMID:20385771

Citation	Shin, ME, Skokotas, A and Winter, E (2010) The Cdk1 and Ime2 protein kinases trigger exit from meiotic prophase in Saccharomyces cerevisiae by inhibiting the Sum1 transcriptional repressor. Mol. Cell. Biol. 30:2996-3003
Abstract	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.
Links	PubMed PMC2876671 Online version:10.1128/MCB.01682-09
Keywords	Binding Sites; CDC2 Protein Kinase/antagonists & inhibitors; CDC2 Protein Kinase/metabolism; CDC28 Protein Kinase, S cerevisiae/antagonists & inhibitors; CDC28 Protein Kinase, S cerevisiae/metabolism; DNA-Binding Proteins/metabolism; Estradiol/pharmacology; Gene Expression Regulation, Fungal/drug effects; Genes, Fungal/genetics; Intracellular Signaling Peptides and Proteins/metabolism; Meiotic Prophase I/drug effects; Mitogen-Activated Protein Kinases/metabolism; Mutation/genetics; Nuclear Proteins/antagonists & inhibitors; Phenotype; Promoter Regions, Genetic/genetics; Protein-Serine-Threonine Kinases/metabolism; Repressor Proteins/antagonists & inhibitors; Saccharomyces cerevisiae/cytology; Saccharomyces cerevisiae/enzymology; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/physiology; Saccharomyces cerevisiae Proteins/antagonists & inhibitors; Saccharomyces cerevisiae Proteins/metabolism; Signal Transduction/drug effects; Spores, Fungal/drug effects; Spores, Fungal/genetics; Transcription Factors/metabolism; Transcription, Genetic/drug effects
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
YEAST:SUM1		GO:0110029: negative regulation of meiosis I	ECO:0000315:		P		Figs. 2 & 4 show that in S. cerevisiae, the sum1 gene is required for preventing sporulation.	complete CACAO 13424
YEAST:SUM1		GO:0001227: DNA-binding transcription repressor activity, RNA polymerase II-specific	ECO:0000315:		F		Figs. 4,5,and 6 show that in S. cerevisiae, Sum1 is required for repressing the NDT80 promoter.	complete CACAO 13429
YEAST:CDK1		GO:0006468: protein phosphorylation	ECO:0000315:		P		Figs. 1 shows that in S. cerevisiae, Cdk1 (also known as CDC28 in Uniprot) is required for repression of Sum1 by phosphorylation.	complete CACAO 13433

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