A stochastic, molecular model of the fission yeast cell cycle: role of the nucleocytoplasmic ratio in cycle time regulation.

We propose a stochastic version of a recently published, deterministic model of the molecular mechanism regulating the mitotic cell cycle of fission yeast, Schizosaccharomyces pombe. Stochasticity is introduced in two ways: (i) by considering the known asymmetry of cell division, which produces daughter cells of slightly different sizes; and (ii) by assuming that the nuclear volumes of the two newborn cells may also differ. In this model, the accumulation of cyclins in the nucleus is proportional to the ratio of cytoplasmic to nuclear volumes. We have simulated the cell-cycle statistics of populations of wild-type cells and of wee1(-) mutant cells. Our results are consistent with well known experimental observations.

[1]  Karen Lundgren,et al.  mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2 , 1991, Cell.

[2]  John J. Tyson,et al.  Modeling the Cell Division Cycle: M-phase Trigger, Oscillations, and Size Control , 1993 .

[3]  J. Tyson,et al.  Is nuclear division in Physarum controlled by a continuous limit cycle oscillator? , 1978, Journal of theoretical biology.

[4]  J. Smith,et al.  Do cells cycle? , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Tyson,et al.  Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte extracts and intact embryos. , 1993, Journal of cell science.

[6]  B. Novák,et al.  The size control of fission yeast revisited. , 1996, Journal of cell science.

[7]  Paul Nurse,et al.  p25rum1 orders S phase and mitosis by acting as an inhibitor of the p34cdc2 mitotic kinase , 1995, Cell.

[8]  W. Sachsenmaier,et al.  Initiation of synchronous mitosis in Physarum polycephalum. A model of the control of cell division in eukariots. , 1972, Experimental cell research.

[9]  J. Tyson,et al.  Modeling M-phase control in Xenopus oocyte extracts: the surveillance mechanism for unreplicated DNA. , 1998, Biophysical chemistry.

[10]  J. Tyson,et al.  Control of nuclear division in Physarum polycephalum: Comparison of cycloheximide pulse treatment, uv irradiation, and heat shock. , 1979, Experimental cell research.

[11]  R. H. Pritchard,et al.  The regulation of cell size and the control of mitosis. , 1975, Journal of theoretical biology.

[12]  Paul Russell,et al.  Negative regulation of mitosis by wee1 +, a gene encoding a protein kinase homolog , 1987, Cell.

[13]  T. Matsumoto A fission yeast homolog of CDC20/p55CDC/Fizzy is required for recovery from DNA damage and genetically interacts with p34cdc2 , 1997, Molecular and cellular biology.

[14]  L. Hartwell Saccharomyces cerevisiae cell cycle. , 1974, Bacteriological reviews.

[15]  M. Dasso,et al.  Completion of DNA replication is monitored by a feedback system that controls the initiation of mitosis in vitro: Studies in Xenopus , 1990, Cell.

[16]  John J. Tyson,et al.  Cell Cycle Controls , 2002 .

[17]  P. Russell,et al.  Pyp3 PTPase acts as a mitotic inducer in fission yeast. , 1992, The EMBO journal.

[18]  Michio Ito,et al.  The Cell Cycle in the Fission Yeast, Schizosaccharomyces pombe . I. Relationship between Cell Size and Cycle Time , 1978 .

[19]  D. Koshland,et al.  An amplified sensitivity arising from covalent modification in biological systems. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Paul Russell,et al.  cdc25 + functions as an inducer in the mitotic control of fission yeast , 1986, Cell.

[21]  E. Powell A NOTE ON KOCH AND SCHAECHTER'S HYPOTHESIS ABOUT GROWTH AND FISSION OF BACTERIA. , 1964, Journal of general microbiology.

[22]  J. A. Smith,et al.  Mammalian cell cycles need two random transitions , 1980, Cell.

[23]  P. Nurse,et al.  Cyclins of the fission yeast Schizosaccharomyces pombe. , 1995, Seminars in cell biology.

[24]  J. Tyson,et al.  Modeling the control of DNA replication in fission yeast. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Paul Nurse,et al.  Genetic control of cell size at cell division in yeast , 1975, Nature.

[26]  S. Moreno,et al.  rum1: a CDK inhibitor regulating G1 progression in fission yeast. , 1996, Trends in cell biology.

[27]  J. Tyson,et al.  Modeling the fission yeast cell cycle: quantized cycle times in wee1- cdc25Delta mutant cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Andrew W. Murray,et al.  The Cell Cycle , 1989 .

[29]  J. Tyson,et al.  Mathematical model for early development of the sea urchin embryo , 2000, Bulletin of mathematical biology.

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

[31]  J. Tyson Modeling the cell division cycle: cdc2 and cyclin interactions. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Tyson,et al.  Sloppy size control of the cell division cycle. , 1986, Journal of theoretical biology.

[33]  A. Murray,et al.  The Cell Cycle: An Introduction , 1993 .

[34]  Katherine C. Chen,et al.  Kinetic analysis of a molecular model of the budding yeast cell cycle. , 2000, Molecular biology of the cell.

[35]  Y. Masui,et al.  Transition of the blastomere cell cycle from cell size-independent to size-dependent control at the midblastula stage in Xenopus laevis. , 2000, The Journal of experimental zoology.

[36]  J. Broach,et al.  The Molecular biology of the yeast saccharomyces, life cycle and inheritance , 1981 .

[37]  J. Tyson,et al.  Size control of cell division. , 1987, Journal of theoretical biology.

[38]  A. Zetterberg,et al.  A quantitative cytochemical investigation of the relationship between cell mass and initiation of DNA synthesis in mouse fibroblasts in vitro. , 1965, Experimental cell research.

[39]  Mitchison Jm My favourite cell: The fission yeast, Schizosaccharomyces pombe , 1990 .

[40]  P. Nurse A Long Twentieth Century of the Cell Cycle and Beyond , 2000, Cell.

[41]  A Goldbeter,et al.  A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[42]  K. Tanaka,et al.  A pcl-like cyclin activates the Res2p-Cdc10p cell cycle "start" transcriptional factor complex in fission yeast. , 2000, Molecular biology of the cell.

[43]  John J. Tyson,et al.  The coordination of cell growth and division — intentional or Incidental? , 1985 .

[44]  P. Nurse Universal control mechanism regulating onset of M-phase , 1990, Nature.

[45]  Robert T. Johnson,et al.  NUCLEO‐CYTOPLASMIC INTERACTIONS IN THE ACHIEVEMENT OF NUCLEAR SYNCHRONY IN DNA SYNTHESIS AND MITOSIS IN MULTINUCLEATE CELLS , 1971, Biological reviews of the Cambridge Philosophical Society.

[46]  P. Nurse,et al.  A quantitative model for the cdc2 control of S phase and mitosis in fission yeast. , 1996, Trends in genetics : TIG.

[47]  S. Moreno,et al.  B‐type cyclins regulate G1 progression in fission yeast in opposition to the p25rum1 cdk inhibitor. , 1996, The EMBO journal.

[48]  A. Nasim,et al.  Molecular biology of the fission yeast , 1989 .

[49]  J. Mitchison 6 – Cell Cycle Growth and Periodicities , 1989 .

[50]  P. Fantes Control of cell size and cycle time in Schizosaccharomyces pombe. , 1977, Journal of cell science.

[51]  P. Thuriaux,et al.  Controls over the timing of DNA replication during the cell cycle of fission yeast. , 1977, Experimental cell research.

[52]  Katherine C. Chen,et al.  Mathematical model of the fission yeast cell cycle with checkpoint controls at the G1/S, G2/M and metaphase/anaphase transitions. , 1998, Biophysical chemistry.

[53]  John J. Tyson,et al.  A stochastic model of cell division (with application to fission yeast) , 1987 .

[54]  A STOCHASTIC MODEL OF THE FISSION YEAST CELL CYCLE , 1996 .

[55]  D. Prescott Relation between cell growth and cell division. III. Changes in nuclear volume and growth rate and prevention of cell division in Amoeba proteus resulting from cytoplasmic amputations. , 1956, Experimental cell research.

[56]  T. Stokke,et al.  Regulation of the start of DNA replication in Schizosaccharomyces pombe. , 1999, Journal of cell science.

[57]  S. Moreno,et al.  The puc1 cyclin regulates the G1 phase of the fission yeast cell cycle in response to cell size. , 2000, Molecular biology of the cell.

[58]  John J. Tyson,et al.  Quantitative analysis of a molecular model of mitotic control in fission yeast , 1995 .

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

[60]  Effects of asymmetric division on a stochastic model of the cell division cycle. , 1989, Mathematical biosciences.

[61]  J. Tyson,et al.  The distributions of cell size and generation time in a model of the cell cycle incorporating size control and random transitions. , 1985, Journal of theoretical biology.

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

[63]  J. Benito,et al.  Regulation of the G1 phase of the cell cycle by periodic stabilization and degradation of the p25rum1 CDK inhibitor , 1998, The EMBO journal.

[64]  W. Donachie,et al.  Relationship between Cell Size and Time of Initiation of DNA Replication , 1968, Nature.