title: Mitotic expression of Spo13 alters M-phase progression and nucleolar localization of Cdc14 in budding yeast.
abstract: Spo13 is a key meiosis-specific regulator required for centromere cohesion and coorientation, and for progression through two nuclear divisions. We previously reported that it causes a G2/M arrest and may delay the transition from late anaphase to G1, when overexpressed in mitosis. Yet its mechanism of action has remained elusive. Here we show that Spo13, which is phosphorylated and stabilized at G2/M in a Cdk/Clb-dependent manner, acts at two stages during mitotic cell division. Spo13 provokes a G2/M arrest that is reversible and largely independent of the Mad2 spindle checkpoint. Since mRNAs whose induction requires Cdc14 activation are reduced, we propose that its anaphase delay results from inhibition of Cdc14 function. Indeed, the Spo13-induced anaphase delay correlates with Cdc14 phosphatase retention in the nucleolus and with cyclin B accumulation, which both impede anaphase exit. At the onset of arrest, Spo13 is primarily associated with the nucleolus, where Cdc14 accumulates. Significantly, overexpression of separase (Esp1), which promotes G2/M and anaphase progression, suppresses Spo13 effects in mitosis, arguing that Spo13 acts upstream or parallel to Esp1. Given that Spo13 overexpression reduces Pds1 and cyclin B degradation, our findings are consistent with a role for Spo13 in regulating APC, which controls both G2/M and anaphase. Similar effects of Spo13 during meiotic MI may prevent cell cycle exit and initiation of DNA replication prior to MII, thereby ensuring two successive chromosome segregation events without an intervening S phase.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Varela
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schlecht
authors.forename: Anca
authors.initials: A
authors.lastname: Moina
authors.forename: James D
authors.initials: JD
authors.lastname: Fackenthal
authors.forename: Brian K
authors.initials: BK
authors.lastname: Washburn
authors.forename: Christa
authors.initials: C
authors.lastname: Niederhauser-Wiederkehr
authors.forename: Monika
authors.initials: M
authors.lastname: Tsai-Pflugfelder
authors.forename: Michael
authors.initials: M
authors.lastname: Primig
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gasser
authors.forename: Rochelle E
authors.initials: RE
authors.lastname: Esposito
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D002466:Cell Nucleolus / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D008938:Mitosis / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; C097192:SPO13 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D018844:Cyclin-Dependent Kinases; D017027:Protein Tyrosine Phosphatases
references.citation: Science. 2004 Jul 23;305(5683):516-9
references.pmid: 15273393
references.citation: Curr Biol. 2001 Apr 3;11(7):508-13
references.pmid: 11413001
references.citation: Cell. 2000 Dec 22;103(7):1155-68
references.pmid: 11163190
references.citation: Dev Cell. 2003 May;4(5):727-39
references.pmid: 12737807
references.citation: Mol Cell Biol. 2005 Jun;25(11):4767-81
references.pmid: 15899877
references.citation: Cell Cycle. 2005 Jan;4(1):109-12
references.pmid: 15611663
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13431-6
references.pmid: 12370439
references.citation: Genetics. 1980 Nov;96(3):567-88
references.pmid: 7021311
references.citation: Cell. 2000 Oct 27;103(3):375-86
references.pmid: 11081625
references.citation: J Cell Biol. 1996 Sep;134(6):1349-63
references.pmid: 8830766
references.citation: Genome Biol. 2010;11(3):R24
references.pmid: 20193063
references.citation: J Theor Biol. 2007 Oct 7;248(3):560-73
references.pmid: 17659305
references.citation: BMC Bioinformatics. 2005 Nov 18;6:275
references.pmid: 16297241
references.citation: Science. 2000 Jul 14;289(5477):300-3
references.pmid: 10894778
references.citation: Cell. 2006 May 19;125(4):719-32
references.pmid: 16713564
references.citation: Cell. 2004 May 14;117(4):455-69
references.pmid: 15137939
references.citation: J Cell Biol. 2005 Jan 31;168(3):375-87
references.pmid: 15684028
references.citation: Mol Cell Biol. 1992 Sep;12(9):3948-58
references.pmid: 1508196
references.citation: Nature. 1999 Apr 29;398(6730):818-23
references.pmid: 10235265
references.citation: Yeast. 1998 Jul;14(10):953-61
references.pmid: 9717241
references.citation: BMC Bioinformatics. 2008 Feb 06;9:86
references.pmid: 18254954
references.citation: EMBO J. 1999 Nov 15;18(22):6448-54
references.pmid: 10562556
references.citation: Nat Cell Biol. 1999 Nov;1(7):438-43
references.pmid: 10559988
references.citation: Genetics. 1989 Sep;123(1):29-43
references.pmid: 2680756
references.citation: Cell. 2008 Apr 18;133(2):280-91
references.pmid: 18423199
references.citation: Curr Biol. 2004 Dec 29;14(24):2183-96
references.pmid: 15620645
references.citation: Dev Cell. 2003 May;4(5):711-26
references.pmid: 12737806
references.citation: Mol Cell Biol. 1998 Oct;18(10):5750-61
references.pmid: 9742092
references.citation: Curr Biol. 2004 Dec 29;14(24):2168-82
references.pmid: 15620644
references.citation: Mol Cell Biol. 2002 Sep;22(18):6417-29
references.pmid: 12192041
references.citation: Proc Natl Acad Sci U S A. 1990 Dec;87(23):9406-10
references.pmid: 2123556
references.citation: Cell. 1999 Jul 9;98(1):91-103
references.pmid: 10412984
references.citation: Cell. 2002 Jan 25;108(2):207-20
references.pmid: 11832211
references.citation: Mol Cell Biol. 1987 Apr;7(4):1425-35
references.pmid: 3299047
references.citation: Genes Dev. 2002 Jul 1;16(13):1672-81
references.pmid: 12101125
references.citation: Mol Cell Biol. 2003 Mar;23(6):2009-16
references.pmid: 12612074
references.citation: Mol Cell. 1998 Dec;2(6):709-18
references.pmid: 9885559
references.citation: Nat Cell Biol. 2003 Mar;5(3):249-54
references.pmid: 12598903
references.citation: Proc Natl Acad Sci U S A. 1982 May;79(9):2986-90
references.pmid: 7045878
references.citation: Dev Cell. 2003 Apr;4(4):535-48
references.pmid: 12689592
references.citation: Curr Biol. 2002 Jul 23;12(14):R482-84
references.pmid: 12176346
references.citation: Genes Dev. 1996 Dec 15;10(24):3081-93
references.pmid: 8985178
references.citation: Cell. 1999 Apr 16;97(2):233-44
references.pmid: 10219244
references.citation: Annu Rev Genet. 2004;38:203-32
references.pmid: 15568976
references.citation: J Cell Biol. 2007 Jun 18;177(6):981-93
references.pmid: 17562791
references.citation: Nature. 2000 Sep 21;407(6802):395-401
references.pmid: 11014197
references.citation: EMBO J. 2009 Jun 3;28(11):1562-75
references.pmid: 19387493
references.citation: J Biol Chem. 2007 Jul 6;282(27):19710-5
references.pmid: 17493939
references.citation: Genetics. 1994 Sep;138(1):47-60
references.pmid: 8001793
references.citation: Mol Cell. 1998 Jul;2(1):65-73
references.pmid: 9702192
references.citation: Genetics. 2000 Aug;155(4):1607-21
references.pmid: 10924460
references.citation: Cell. 2004 May 14;117(4):471-82
references.pmid: 15137940
references.citation: Genetics. 1980 Nov;96(3):589-611
references.pmid: 7021312
references.citation: Mol Biol Cell. 2008 May;19(5):2193-207
references.pmid: 18305101
references.citation: Genes Dev. 2002 Jul 1;16(13):1659-71
references.pmid: 12101124
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D457-62
references.pmid: 17145711
references.citation: Mol Gen Genet. 1999 Sep;262(2):275-82
references.pmid: 10517323
references.citation: Genes Dev. 1999 Aug 1;13(15):1936-49
references.pmid: 10444592