Abstract
Much scientific research has focused on characterising regulatory pathways and mechanisms responsible for cell integrity, growth and division. This area of study is of direct relevance to human medicine as uncontrolled growth and division underlies many diseases, most strikingly cancer. In cancer cells, normal regulatory mechanisms for growth and division are often altered, or even fail to exist. This review summarises the mechanisms that control the genes and gene products regulating cytokinesis and cell separation in the fission yeast Schizosaccharomyces pombe, as well as highlighting conserved aspects in the budding yeast Saccharomyces cerevisiae and higher eukaryotes. Particular emphasis is put on the role of gene expression, the Polo-like kinases (Plks), and the signal transduction pathways that control these processes.
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Alonso-Nunez ML, An H, Martin-Cuadrado AB, Mehta S, Petit C, Sipiczki M, del Rey F, Gould KL, de Aldana CR (2005) Ace2p controls the expression of genes required for cell separation in Schizosaccharomyces pombe. Mol Biol Cell 16:2003–2017
Alvarez B, Martinez-A C, Burgering BM, Carrera AC (2001) Forkhead transcription factors contribute to execution of the mitotic programme in mammals. Nature 413:744–747
Anderson M, Ng SS, Marchesi V, MacIver FH, Stevens FE, Riddell T, Glover DM, Hagan IM, McInerny CJ (2002) Plo1+ regulates gene transcription at the M-G1 interval during the fission yeast mitotic cell cycle. EMBO J 21:5745–5755
Bähler J (2005) Cell-cycle control of gene expression in budding and fission yeast. Annu Rev Genet 39:69–94
Bähler J, Steever AB, Wheatley S, Wang Y, Pringle JR, Gould KL, McCollum D (1998) Role of polo kinase and Mid1p in determining the site of cell division in fission yeast. J Cell Biol 143:1603–1616
Balasubramanian MK, McCollum D, Chang L, Wong KC, Naqvi NI, He X, Sazer S, Gould KL (1998) Isolation and characterization of new fission yeast cytokinesis mutants. Genetics 149:1265–1275
Balasubramanian MK, McCollum D, Surana U (2000) Tying the knot: linking cytokinesis to the nuclear cycle. J Cell Sci 113:1503–1513
Bardin AJ, Amon A (2001) Men and sin: what’s the difference? Nat Rev Mol Cell Biol 2:815–826
Breeden LL (2000) Cyclin transcription: timing is everything. Curr Biol 10:586–588
Buck V, Ng SS, Ruiz-Garcia AB, Papadopoulou K, Bhatti S, Samuel JM, Anderson M, Millar JB, McInerny CJ (2004) Fkh2p and Sep1p regulate mitotic gene transcription in fission yeast. J Cell Sci 117:5623–5632
Bulmer R, Pic-Taylor A, Whitehall SK, Martin KA, Millar JB, Quinn J, Morgan BA (2004) The forkhead transcription factor Fkh2 regulates the cell division cycle of Schizosaccharomyces pombe. Eukaryot Cell 3:944–954
Carmena M, Riparbelli MG, Minestrini G, Tavares AM, Adams R, Callaini G, Glover DM (1998) Drosophila polo kinase is required for cytokinesis. J Cell Biol 143:659–671
Chang F, Nurse P (1996) How fission yeast fission in the middle. Cell 84:191–194
Cho RJ, Campbell MJ, Winzeler EA, Steinmetz L, Conway A, Wodicka L, Wolfsberg TG, Gabrielian AE, Landsman D, Lockhart DJ, Davis RW (1998) A genome-wide transcriptional analyses of the mitotic cell cycle. Mol Cell 2:65–73
Daga RR, Lahoz A, Munoz MJ, Moreno S, Jimenez J (2005) Etd1p is a novel protein that links the SIN cascade with cytokinesis. EMBO J 24:2436–2446
Fankhauser C, Simanis V (1994) The cdc7 protein kinase is a dosage dependent regulator of septum formation in fission yeast. EMBO J 13:3011–3019
Fankhauser C, Reymond A, Cerutti L, Utzig S, Hofmann K, Simanis V (1995) The S. pombe cdc15 gene is a key element in the reorganization of F-actin at mitosis. Cell 82:435–444
Glover DM (1991) Mitosis in the Drosophila embryo—in and out of control. Trends Genet 7:125–132
Goffeau A et al (1996) Life with 6000 genes. Science 274:546, 563–577
Gould KL (2003) Protein kinases driving the cell cycle. In: Egel R (ed) The molecular biology of Schizosaccharomyces pombe. Springer, Berlin Heidelberg New York, pp 27–40
Grallert A, Hagan IM (2002) Schizosaccharomyces pombe NIMA-related kinase Fin1, regulates spindle formation and an affinity of Polo for the SPB. EMBO J 21:3096–3107
Hagan IM, Hyams JS (1988) The use of cell division cycle mutants to investigate the control of microtubule distribution in the fission yeast Schizosaccharomyces pombe. J Cell Sci 89:343–357
Hoffmann I, Clarke PR, Marcote MJ, Karsenti E, Draetta G (1993) Phosphorylation and activation of human cdc25C by Cdc2-cyclin B and its involvement in the self amplification of MPF at mitosis. EMBO J 12:53–63
Hollenhorst PC, Bose ME, Mielke MR, Muller U, Fox CA (2000) Forkhead genes in transcriptional silencing, cell morphology and the cell cycle. Overlapping and distinct functions for FKH1 and FKH2 in Saccharomyces cerevisiae. Genetics 154:1533–1548
Hollenhorst PC, Pietz G, Fox CA (2001) Mechanisms controlling differential promoter-occupancy by yeast forkhead proteins Fkh1p and Fkh2p: implication for regulating the cell cycle and differentiation. Genes Dev 15:2445–2456
Kim SH, Lin DP, Matsumoto S, Kitazono A, Matsumoto T (1998) Fission yeast Slp1: an effector of the Mad2-dependent spindle checkpoint. Science 279:1045–1047
Krien MJ, West RR, John UP, Koniaras K, McIntosh JR, O’Connell MJ (2002) The fission yeast NIMA kinase Fin1p is required for spindle function and nuclear envelope integrity. EMBO J 21:1713–1722
Kumagai A, Dunphy WG (1996) Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts. Science 273:1377–1380
Kumar R, Reynolds DM, Shevchenko A, Shevchenko A, Goldstone SD, Dalton S (2000) Forkhead transcription factors, Fkh1p and Fkh2p, collaborate with Mcm1p to control transcription required for M-phase. Curr Biol 10:896–906
Le Goff X, Utzig S, Simanis V (1999) Controlling septation in fission yeast: finding the middle, and timing it right. Curr Genet 35:571–584
Lee KM, Miklos I, Du H, Watt S, Szilagyi Z, Saiz JE, Madabhushi R, Penkett CJ, Sipiczki M, Bähler J, Fisher RP (2005) Impairment of the TFII associated CDK-activating kinase selectivity affects cell cycle-regulated gene expression in fission yeast. Mol Biol Cell 16:2734–2745
Martin-Cuadrado AB, Duenas E, Sipiczki M, Vazquez de Aldana CR, del Rey F (2003) The endo-β-1,3-glucanase eng1p is required for dissolution of the primary septum during cell separation in S. pombe. J Cell Sci 116:1689–1698
McCollum D, Gould KL (2001) Timing is everything: regulation of mitotic exit and cytokinesis by the MEN and SIN. Trends Cell Biol 11:89–95
McInerny CJ (2004) Cell cycle-regulated transcription in fission yeast. Biochem Soc Trans 32:967–972
McInerny CJ, Partridge JF, Mikesell GE, Creemer DP, Breeden LL (1997) A novel Mcm1-dependent element in the SWI4, CLN3, CDC6 and CDC47 promoters activates M/G1-specific transcription. Genes Dev 11:1277–1288
Minet M, Nurse P, Thuriaux P, Mitchison JM (1979) Uncontrolled septation in a cell division cycle mutant of the fission yeast Schizosaccharomyces pombe. J Bacteriol 137:440–446
Molz L, Booher R, Young P, Beach D (1989) cdc2 and the regulation of mitosis: six interacting mcs genes. Genetics 122:773–782
Moser BA, Russell P (2000) Cell cycle regulation in Schizosaccharomyces pombe. Curr Opin Microbiol 3:631–636
Mulvihill DP, Hyams JS (2003) Role of the two type II myosins, Myo2 and Myp2, in cytokinetic actomyosin ring formation and function in fission yeast. Cell Motil Cytoskeleton 54:208–216
Mulvihill DP, Petersen J, Ohkura H, Glover DM, Hagan IM (1999) Plo1 kinase recruitment to the spindle pole body and its role in cell division in Schizosaccharomyces pombe. Mol Biol Cell 10:2771–2785
Mundt KE, Golsteyn RM, Lane HA, Nigg EA (1997) On the regulation and function of human polo-like kinase 1 (PLK1): effects of overexpression on cell cycle progression. Biochem Biophys Res Commun 239:377–385
Ohkura H, Hagan IM, Glover DM (1995) The conserved Scizosaccharomyces pombe kinase plo1, required to form a bipolar spindle, the actin ring, and septum, can drive septum formation in G1 and G2 cells. Genes Dev 9:1059–1073
Oliva A, Rosebrock A, Ferrezuelo F, Pyne S, Chen H, Skiena S, Futcher B, Leatherwood J (2005) The cell cycle-regulated genes of Schizosaccharomyces pombe. PLoS Biol 3:e225
Peng X, Karuturi RK, Miller LD, Lin K, Jia Y, Kondu P, Wang L, Wong LS, Liu ET, Balasubramanian MK, Liu J (2005) Identification of cell cycle-regulated genes in fission yeast. Mol Biol Cell 16:1026–1042
Petit CS, Mehta S, Roberts RH, Gould KL (2005) Ace2p contributes to fission yeast septin ring assembly by regulating mid2 + expression. J Cell Sci 118:5731–5742
Pic A, Lim FL, Ross SJ, Veal EA, Johnson AL, Sultan MR, West AG, Johnston LH, Sharrocks AD, Morgan BA (2000) The forkhead protein Fkh2 is a component of the yeast cell cycle transcription factor SFF. EMBO J 19:3750–3761
Reynolds N, Ohkura H (2003) Polo boxes form a single functional domain that mediate interactions with multiple proteins in fission yeast polo kinase. J Cell Sci 116:1377–1387
Rustici G, Mata J, Kivinen K, Lio P, Penkett CJ, Burns G, Hayles J, Brazma A, Nurse P, Bähler J (2004) Periodic gene expression program of the fission yeast cell cycle. Nat Genet 36:809–817
Satterwhite LL, Pollard TD (1992) Cytokinesis. Curr Opin Cell Biol 4:43–52
Schmidt S, Sohrmann M, Hofmann K, Woollard A, Simanis V (1997) The Spg1p GTPase is an essential, dosage-dependent inducer of septum formation in Schizosaccharomyces pombe. Genes Dev 11:1519–1534
Schweitzer B, Philippsen P (1991) CDC15, an essential cell cycle gene in Saccharomyces cerevisiae, encodes a protein kinase domain. Yeast 7:265–273
Sharrocks AD (2002) Modern approaches in studying gene expression. Methods 26:215–216
Shirayama M, Matsui Y, Toh-E A (1994) The yeast TEM1 gene, which encodes a GTP-binding protein, is involved in termination of M phase. Mol Cell Biol 14:7476–7482
Simon I, Barnett J, Hannett N, Harbison CT, Rinaldi NJ, Volkert TL, Wyrick JJ, Zeitlinger J, Gifford DK, Jaakkola TS, Young RA (2001) Serial regulation of transcriptional regulator in the yeast cell cycle. Cell 106:697–708
Sohrmann M, Fankhauser C, Brodbeck C, Simanis V (1996) The dmf1/mid1 gene is essential for correct positioning of the division septum in fission yeast. Genes Dev 10:2707–2719
Song K, Mach KE, Chen CY, Reynolds T, Albright CF (1996) A novel suppressor of ras1 in fission yeast, byr4, is a dosage-dependent inhibitor of cytokinesis. J Cell Biol 133:1307–1319
Spellman PT, Sherlock G, Zhang MQ, Iyer VR, Anders K, Eisen MB, Brown PO, Botstein D, Futcher B (1998) Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9:3273–3297
Tanaka K, Petersen J, MacIver F, Mulvihill DP, Glover DM, Hagan IM (2001) The role of Plo1 kinase in mitotic commitment and septation in Schizosaccharomyces pombe. EMBO J 20:1259–1270
Tasto JJ, Morrell JL, Gould KL (2003) An anillin homologue, Mid2p, acts during fission yeast cytokinesis to organize the septin ring and promote cell separation. J Cell Biol 160:1093–1103
Toyn JH, Araki H, Sugino A, Johnston LH (1991) The cell cycle-regulated budding yeast gene DBF2, encoding a putative protein kinase, has a homologue that is not under cell cycle control. Gene 104:63–70
Treisman R (1994) Ternary complex factors: growth factor regulated transcriptional activators. Curr Opin Genet Dev 4:96–101
Whitmarsh AJ, Davis RJ (2000) Regulation of transcription factor function by phosphorylation. Cell Mol Life Sci 57:1172–1183
Wood V, et al (2002) The genome sequence of Schizosaccharomyces pombe. Nature 415:871–880
Zilahi E, Salimova E, Simanis V, Sipiczki M (2000) The S. pombe sep1 gene encodes a nuclear protein that is required for periodic expression of the cdc15 gene. FEBS Lett 481:105–108
van Zyl W, Huang W, Sneddon AA, Stark M, Camier S, Werner M, Marck C, Sentenac A, Broach JR (1992) Inactivation of the protein phosphatase 2A regulatory subunit results in morphological and transcriptional defects in Saccharomyces cerevisiae. Mol Cell Biol 12:4946–4959
Acknowledgements
Work in the laboratory is supported by the Wellcome Trust. K.P. is a Wellcome Trust Student. We thank Chris MacDonald for commenting on the manuscript.
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Communicated by P. Sunnerhagen
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Ng, S.S., Papadopoulou, K. & McInerny, C.J. Regulation of gene expression and cell division by Polo-like kinases. Curr Genet 50, 73–80 (2006). https://doi.org/10.1007/s00294-006-0077-y
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DOI: https://doi.org/10.1007/s00294-006-0077-y