title: The Cdk1 and Ime2 protein kinases trigger exit from meiotic prophase in Saccharomyces cerevisiae by inhibiting the Sum1 transcriptional repressor.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Shin
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Skokotas
authors.forename: Edward
authors.initials: E
authors.lastname: Winter
mesh_terms: 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
chemical_list: 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
references.citation: Genes Dev. 2003 Jun 15;17(12):1524-39
references.pmid: 12783856
references.citation: Genes Dev. 2001 Apr 15;15(8):955-67
references.pmid: 11316790
references.citation: Mol Cell Biol. 1995 Dec;15(12):6572-81
references.pmid: 8524222
references.citation: Genes Dev. 1998 Sep 1;12(17):2698-710
references.pmid: 9732268
references.citation: EMBO J. 1997 Mar 17;16(6):1305-17
references.pmid: 9135146
references.citation: Mol Cell. 2007 Mar 9;25(5):689-702
references.pmid: 17349956
references.citation: EMBO J. 1999 Jan 15;18(2):320-9
references.pmid: 9889189
references.citation: Curr Biol. 2006 Mar 21;16(6):R217-28
references.pmid: 16546077
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12187-92
references.pmid: 11035815
references.citation: Mol Cell Biol. 2003 Jul;23(14):4814-25
references.pmid: 12832469
references.citation: Mol Cell Biol. 2009 Aug;29(16):4352-62
references.pmid: 19528232
references.citation: Nat Genet. 2000 Dec;26(4):415-23
references.pmid: 11101837
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16934-9
references.pmid: 17939997
references.citation: Genetics. 1999 Apr;151(4):1327-40
references.pmid: 10101160
references.citation: EMBO J. 2000 Dec 1;19(23):6489-97
references.pmid: 11101521
references.citation: Genetics. 2005 Nov;171(3):901-11
references.pmid: 16079231
references.citation: J Cell Biochem. 2004 Aug 1;92(5):1025-33
references.pmid: 15258924
references.citation: Microbiol Rev. 1994 Mar;58(1):56-70
references.pmid: 8177171
references.citation: Mol Cell Biol. 2002 Jan;22(1):57-68
references.pmid: 11739722
references.citation: Mol Cell. 1998 Apr;1(5):685-96
references.pmid: 9660952
references.citation: Mol Cell Biol. 2003 Oct;23(19):7044-54
references.pmid: 12972620
references.citation: EMBO J. 1999 Nov 15;18(22):6448-54
references.pmid: 10562556
references.citation: Curr Opin Cell Biol. 2000 Jun;12(3):334-9
references.pmid: 10801467
references.citation: Trends Genet. 2000 Sep;16(9):395-403
references.pmid: 10973068
references.citation: Cell. 2008 Apr 18;133(2):280-91
references.pmid: 18423199
references.citation: Mol Cell Biol. 1998 Oct;18(10):5750-61
references.pmid: 9742092
references.citation: Int Rev Cytol. 2003;224:111-71
references.pmid: 12722950
references.citation: Mol Cell Biol. 1998 Oct;18(10):5970-80
references.pmid: 9742114
references.citation: Mol Cell Biol. 2002 Sep;22(18):6417-29
references.pmid: 12192041
references.citation: Nature. 2003 Oct 16;425(6959):737-41
references.pmid: 14562106
references.citation: Mol Cell Biol. 2003 Mar;23(6):2009-16
references.pmid: 12612074
references.citation: Bioessays. 2009 Feb;31(2):169-77
references.pmid: 19204989
references.citation: Science. 1998 Oct 23;282(5389):699-705
references.pmid: 9784122
references.citation: Genetics. 2009 Feb;181(2):511-23
references.pmid: 19087957
references.citation: Science. 1998 Sep 18;281(5384):1854-7
references.pmid: 9743499
references.citation: Genes Dev. 2008 Oct 1;22(19):2627-32
references.pmid: 18832066
references.citation: EMBO J. 1995 Oct 2;14(19):4803-13
references.pmid: 7588610
references.citation: Biochemistry. 2007 Jan 9;46(1):271-8
references.pmid: 17198398
references.citation: Genetics. 2004 May;167(1):51-63
references.pmid: 15166136
references.citation: Cell. 2001 Dec 28;107(7):819-22
references.pmid: 11779457