Flp1, a fission yeast orthologue of the s. cerevisiae CDC14 gene, is not required for cyclin degradation or rum1p stabilisation at the end of mitosis.

In Saccharomyces cerevisiae, the phosphoprotein phosphatase Cdc14p plays a central role in exit from mitosis, by promoting B-type cyclin degradation and allowing accumulation of the cyclin-dependent kinase inhibitor Sic1p. Cdc14p is sequestered in the nucleolus during interphase, from where it is released at the end of mitosis, dependent upon mitotic exit network function. The CDC14 gene is essential and loss-of-function mutants arrest at the end of mitosis. We have identified a fission yeast orthologue of CDC14 through database searches. A Schizosaccharomyces pombe flp1 (cdc fourteen-like-phosphatase) null mutant is viable, divides at a reduced size and shows defects in septation. flp1p is not the essential effector of the S. pombe septation initiation network, but may potentiate signalling of the onset of septation. In contrast to S. cerevisiae Cdc14p, flp1p is not required for the accumulation or destruction of the B-type cyclin cdc13p, the cyclin-dependent kinase inhibitor rum1p, or for dephosphorylation of the APC/C specificity factor ste9p in G1. Like its budding yeast counterpart, flp1p is restricted to the nucleolus until mitosis, when it is dispersed through the nucleus. In contrast to S. cerevisiae Cdc14p, flp1p is also present on the mitotic spindle and contractile ring. The potential roles of flp1p in cell cycle control are discussed.

[1]  P. Thuriaux,et al.  Uncontrolled septation in a cell division cycle mutant of the fission yeast Schizosaccharomyces pombe , 1979, Journal of bacteriology.

[2]  P. Fantes.  Isolation of cell size mutants of a fission yeast by a new selective method: characterization of mutants and implications for division control mechanisms , 1981, Journal of bacteriology.

[3]  P. Fantes.  Control of timing of cell cycle events in fission yeast by the wee 1+ gene , 1983, Nature.

[4]  J. Marks,et al.  Growth Polarity and Cytokinesis in Fission Yeast: The Role of the Cytoskeleton , 1986, Journal of Cell Science.

[5]  P. Nurse,et al.  Negative Regulation of Mitosis , 1987 .

[6]  P. Russell,et al.  The mitotic inducer nim1 + functions in a regulatory network of protein kinase homologs controlling the initiation of mitosis , 1987, Cell.

[7]  I. Hagan,et al.  The use of cell division cycle mutants to investigate the control of microtubule distribution in the fission yeast Schizosaccharomyces pombe. , 1988, Journal of cell science.

[8]  Sergio Moreno,et al.  Regulation of p34cdc2 protein kinase during mitosis , 1989, Cell.

[9]  T. Toda,et al.  Essential roles of the RNA polymerase I largest subunit and DNA topoisomerases in the formation of fission yeast nucleolus , 1989, The Journal of cell biology.

[10]  D. Beach,et al.  Fission yeast cdc25 is a cell-cycle regulated protein. , 1990, Biochemical and biophysical research communications.

[11]  P. Nurse,et al.  Mutation of fission yeast cell cycle control genes abolishes dependence of mitosis on DNA replication , 1990, Cell.

[12]  J. Potashkin,et al.  Differential distribution of factors involved in pre-mRNA processing in the yeast cell nucleus , 1990, Molecular and cellular biology.

[13]  Sergio Moreno,et al.  Regulation of mitosis by cyclic accumulation of p80cdc25 mitotic inducer in fission yeast , 1990, Nature.

[14]  G. Blobel,et al.  Isolation and sequencing of NOP1. A yeast gene encoding a nucleolar protein homologous to a human autoimmune antigen. , 1990, The Journal of biological chemistry.

[15]  D. Beach,et al.  Distinct nuclear and spindle pole body populations of cyclin–cdc2 in fission yeast , 1990, Nature.

[16]  G. Blobel,et al.  cDNA cloning and sequencing of human fibrillarin, a conserved nucleolar protein recognized by autoimmune antisera. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[17]  D. Weilguny,et al.  New vectors in fission yeast: application for cloning the his2 gene. , 1991, Gene.

[18]  S. Moreno,et al.  Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. , 1991, Methods in enzymology.

[19]  H. Xu,et al.  CDC14 of Saccharomyces cerevisiae. Cloning, sequence analysis, and transcription during the cell cycle. , 1992, The Journal of biological chemistry.

[20]  A. Carr,et al.  Versatile shuttle vectors and genomic libraries for use with Schizosaccharomyces pombe. , 1992, Gene.

[21]  C. Fankhauser,et al.  The Schizosaccharomyces pombe cdc14 gene is required for septum formation and can also inhibit nuclear division. , 1993, Molecular biology of the cell.

[22]  P. Russell,et al.  Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase , 1993, Nature.

[23]  A. Reymond,et al.  The S. pombe cdc16 gene is required both for maintenance of p34cdc2 kinase activity and regulation of septum formation: a link between mitosis and cytokinesis? , 1993, The EMBO journal.

[24]  K. Maundrell,et al.  TATA box mutations in the Schizosaccharomyces pombe nmt1 promoter affect transcription efficiency but not the transcription start point or thiamine repressibility. , 1993, Gene.

[25]  C. Fankhauser,et al.  The cdc7 protein kinase is a dosage dependent regulator of septum formation in fission yeast. , 1994, The EMBO journal.

[26]  M. Yanagida,et al.  The product of the spindle formation gene sad1+ associates with the fission yeast spindle pole body and is essential for viability , 1995, The Journal of cell biology.

[27]  D. Glover,et al.  The conserved Schizosaccharomyces pombe kinase plo1, required to form a bipolar spindle, the actin ring, and septum, can drive septum formation in G1 and G2 cells. , 1995, Genes & development.

[28]  A. Reymond,et al.  The S. pombe cdc15 gene is a key element in the reorganization of F-actin at mitosis , 1995, Cell.

[29]  C. Y. Chen,et al.  A novel suppressor of ras1 in fission yeast, byr4, is a dosage- dependent inhibitor of cytokinesis , 1996, The Journal of cell biology.

[30]  P. Russell,et al.  Spatial organization of the Nim1-Wee1-Cdc2 mitotic control network in Schizosaccharomyces pombe. , 1996, Molecular biology of the cell.

[31]  M. Sohrmann,et al.  The dmf1/mid1 gene is essential for correct positioning of the division septum in fission yeast. , 1996, Genes & development.

[32]  J. Mitchison,et al.  The kinetics of the B cyclin p56cdc13 and the phosphatase p80cdc25 during the cell cycle of the fission yeast Schizosaccharomyces pombe. , 1996, Journal of cell science.

[33]  U. Moens,et al.  Human polyomavirus BK and immunogenicity of mammalian DNA: a conceptual framework. , 1997, Methods.

[34]  H. Murakami,et al.  A WD repeat protein controls the cell cycle and differentiation by negatively regulating Cdc2/B-type cyclin complexes. , 1997, Molecular biology of the cell.

[35]  S. Sazer,et al.  The Schizosaccharomyces pombe spindle checkpoint protein mad2p blocks anaphase and genetically interacts with the anaphase-promoting complex. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[36]  G S Taylor,et al.  The Activity of Cdc14p, an Oligomeric Dual Specificity Protein Phosphatase from Saccharomyces cerevisiae, Is Required for Cell Cycle Progression* , 1997, The Journal of Biological Chemistry.

[37]  S. Moreno,et al.  Cloning cell cycle regulatory genes by transcomplementation in yeast. , 1997, Methods in enzymology.

[38]  K. Gould,et al.  Cytokinesis in fission yeast Schizosaccharomyces pombe. , 1997, Methods in enzymology.

[39]  P. Russell,et al.  Nif1, a novel mitotic inhibitor in Schizosaccharomyces pombe , 1997, The EMBO journal.

[40]  M. Sohrmann,et al.  The Spg1p GTPase is an essential, dosage-dependent inducer of septum formation in Schizosaccharomyces pombe. , 1997, Genes & development.

[41]  P. Russell,et al.  Regulation of Schizosaccharomyces pombe Wee1 Tyrosine Kinase* , 1997, The Journal of Biological Chemistry.

[42]  J. Dixon,et al.  A Family of Putative Tumor Suppressors Is Structurally and Functionally Conserved in Humans and Yeast* , 1997, The Journal of Biological Chemistry.

[43]  G. Taylor,et al.  The Activity of Cdc 14 p , an Oligomeric Dual Specificity Protein Phosphatase from Saccharomyces cerevisiae , Is Required for Cell Cycle Progression , 1997 .

[44]  M. Tyers,et al.  The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation. , 1998, Molecular cell.

[45]  M. Balasubramanian,et al.  Rng2p, a protein required for cytokinesis in fission yeast, is a component of the actomyosin ring and the spindle pole body , 1998, Current Biology.

[46]  K. Gould,et al.  Role of Polo Kinase and Mid1p in Determining the Site of Cell Division in Fission Yeast , 1998, The Journal of cell biology.

[47]  K. Gould,et al.  Isolation and characterization of new fission yeast cytokinesis mutants. , 1998, Genetics.

[48]  P. Russell,et al.  The protein kinase Cdr2, related to Nim1/Cdr1 mitotic inducer, regulates the onset of mitosis in fission yeast. , 1998, Molecular biology of the cell.

[49]  K. Furge,et al.  Byr4 and Cdc16 form a two-component GTPase-activating protein for the Spg1 GTPase that controls septation in fission yeast , 1998, Current Biology.

[50]  P. Philippsen,et al.  Heterologous modules for efficient and versatile PCR‐based gene targeting in Schizosaccharomyces pombe , 1998, Yeast.

[51]  L. Johnston,et al.  DNA replication is completed in Saccharomyces cerevisiae cells that lack functional Cdc14, a dual-specificity protein phosphatase , 1998, Molecular and General Genetics MGG.

[52]  K. Kitamura,et al.  Fission yeast Ste9, a homolog of Hct1/Cdh1 and Fizzy-related, is a novel negative regulator of cell cycle progression during G1-phase. , 1998, Molecular biology of the cell.

[53]  M. Jones,et al.  Mph1, a member of the Mps1-like family of dual specificity protein kinases, is required for the spindle checkpoint in S. pombe. , 1998, Journal of cell science.

[54]  K. Gould,et al.  The cdr2(+) gene encodes a regulator of G2/M progression and cytokinesis in Schizosaccharomyces pombe. , 1998, Molecular biology of the cell.

[55]  D O Morgan,et al.  A late mitotic regulatory network controlling cyclin destruction in Saccharomyces cerevisiae. , 1998, Molecular biology of the cell.

[56]  M. Sohrmann,et al.  Asymmetric segregation on spindle poles of the Schizosaccharomyces pombe septum-inducing protein kinase Cdc7p. , 1998, Genes & development.

[57]  Angelika Amon,et al.  Cfi1 prevents premature exit from mitosis by anchoring Cdc14 phosphatase in the nucleolus , 1999, Nature.

[58]  Attila Tóth,et al.  APCCdc20 promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5 , 1999, Nature.

[59]  Daniel P. Mulvihill,et al.  Plo1 kinase recruitment to the spindle pole body and its role in cell division in Schizosaccharomyces pombe. , 1999, Molecular biology of the cell.

[60]  B. Novák,et al.  Mitotic control in the absence of cdc25 mitotic inducer in fission yeast. , 1999, Journal of cell science.

[61]  H. Piwnica-Worms,et al.  DNA Damage and Replication Checkpoints in Fission Yeast Require Nuclear Exclusion of the Cdc25 Phosphatase via 14-3-3 Binding , 1999, Molecular and Cellular Biology.

[62]  David O. Morgan,et al.  Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase Cdc28 and the phosphatase Cdc14 , 1999, Current Biology.

[63]  Anna Shevchenko,et al.  Exit from Mitosis Is Triggered by Tem1-Dependent Release of the Protein Phosphatase Cdc14 from Nucleolar RENT Complex , 1999, Cell.

[64]  A. Straight,et al.  Net1, a Sir2-Associated Nucleolar Protein Required for rDNA Silencing and Nucleolar Integrity , 1999, Cell.

[65]  V. Simanis,et al.  Controlling septation in fission yeast: finding the middle, and timing it right , 1999, Current Genetics.

[66]  A. Woollard,et al.  Analysis of the cps1 gene provides evidence for a septation checkpoint in Schizosaccharomyces pombe , 1999, Molecular and General Genetics MGG.

[67]  M. Morphew,et al.  Sid2p, a Spindle Pole Body Kinase That Regulates the Onset of Cytokinesis , 1999, The Journal of cell biology.

[68]  L. Cerutti,et al.  Asymmetry of the spindle pole bodies and spg1p GAP segregation during mitosis in fission yeast. , 1999, Journal of cell science.

[69]  L. Cerutti,et al.  Bypass of the requirement for cdc16p GAP function in Schizosaccharomyces pombe by mutation of the septation initiation network genes , 2000, Archives of Microbiology.

[70]  U. Surana,et al.  Tying the knot: linking cytokinesis to the nuclear cycle. , 2000, Journal of cell science.

[71]  H. Wang,et al.  A checkpoint that monitors cytokinesis in Schizosaccharomyces pombe. , 2000, Journal of cell science.

[72]  S. Jaspersen,et al.  Cdc14 activates Cdc15 to promote mitotic exit in budding yeast , 2000, Current Biology.

[73]  M. Hoyt.  Exit from Mitosis Spindle Pole Power , 2000, Cell.

[74]  M. Sohrmann,et al.  The S. pombe orthologue of the S. cerevisiae mob1 gene is essential and functions in signalling the onset of septum formation. , 2000, Journal of cell science.

[75]  P. Nurse,et al.  Fission yeast Fizzy‐related protein srw1p is a G1‐specific promoter of mitotic cyclin B degradation , 2000, The EMBO journal.

[76]  K. Gould,et al.  The role of the Sid1p kinase and Cdc14p in regulating the onset of cytokinesis in fission yeast , 2000, The EMBO journal.

[77]  K. Sawin.  Cytokinesis: Sid signals septation , 2000, Current Biology.

[78]  K. Gould,et al.  Sid4p is required to localize components of the septation initiation pathway to the spindle pole body in fission yeast. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[79]  D. McCollum,et al.  Mob1p interacts with the Sid2p kinase and is required for cytokinesis in fission yeast , 2000, Current Biology.

[80]  S. Moreno,et al.  APCste9/srw1 promotes degradation of mitotic cyclins in G1 and is inhibited by cdc2 phosphorylation , 2000, The EMBO journal.