Molecular Network Dynamics of Cell Cycle Control: Periodicity of Start and Finish.

The cell division cycle is controlled by a complex regulatory network which ensures that the phases of the cell cycle are executed in the right order. This regulatory network receives signals from the environment, monitors the state of the DNA, and decides timings of cell cycle events. The underlying transcriptional and post-translational regulatory interactions lead to complex dynamical responses, such as the oscillations in the levels of cell cycle proteins driven by intertwined biochemical reactions. A cell moves between different phases of its cycle similar to a dynamical system switching between its steady states. The complex molecular network driving these phases has been investigated in previous computational systems biology studies. Here, we review the critical physiological and molecular transitions that occur in the cell cycle and discuss the role of mathematical modeling in elucidating these transitions and understand cell cycle synchronization.

[1]  John J. Tyson,et al.  Bringing cartoons to life , 2007, Nature.

[2]  P. Mazzarello.  A unifying concept: the history of cell theory , 1999, Nature Cell Biology.

[3]  Denis Thieffry,et al.  Logical modelling of cell cycle control in eukaryotes: a comparative study. , 2009, Molecular bioSystems.

[4]  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.

[5]  John J. Tyson,et al.  Irreversible cell-cycle transitions are due to systems-level feedback , 2007, Nature Cell Biology.

[6]  F. Cross,et al.  Two redundant oscillatory mechanisms in the yeast cell cycle. , 2003, Developmental cell.

[7]  Bela Novak,et al.  Downregulation of PP2ACdc55 Phosphatase by Separase Initiates Mitotic Exit in Budding Yeast , 2006, Cell.

[8]  Jiri Bartek,et al.  Cell-cycle checkpoints and cancer , 2004, Nature.

[9]  Clifford A. Shaffer,et al.  Multistate Model Builder (MSMB): a flexible editor for compact biochemical models , 2014, BMC Systems Biology.

[10]  Marc W Kirschner,et al.  The Meaning of Systems Biology , 2005, Cell.

[11]  F. Cross,et al.  Forced periodic expression of G1 cyclins phase-locks the budding yeast cell cycle , 2009, Proceedings of the National Academy of Sciences.

[12]  J. Schaber,et al.  Model-based inference of biochemical parameters and dynamic properties of microbial signal transduction networks. , 2011, Current opinion in biotechnology.

[13]  Andrea Ciliberto,et al.  A quantitative systems view of the spindle assembly checkpoint , 2009, The EMBO journal.

[14]  L. Hartwell,et al.  Checkpoints: controls that ensure the order of cell cycle events. , 1989, Science.

[15]  P. O'Connor,et al.  Methods for Synchronizing Cells at Specific Stages of the Cell Cycle , 1998, Current protocols in cell biology.

[16]  Radu Mateescu,et al.  Temporal logic patterns for querying dynamic models of cellular interaction networks , 2008, ECCB.

[17]  Attila Csikász-Nagy,et al.  The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation , 2012, Nature Communications.

[18]  Michael Hucka,et al.  Escalating model sizes and complexities call for standardized forms of representation , 2005, Molecular systems biology.

[19]  K. Nasmyth.  A Prize for Proliferation , 2001, Cell.

[20]  Attila Csikász-Nagy,et al.  Analysis of a generic model of eukaryotic cell-cycle regulation. , 2006, Biophysical journal.

[21]  Teeraphan Laomettachit,et al.  Mathematical modeling approaches for dynamical analysis of protein regulatory networks with applications to the budding yeast cell cycle and the circadian rhythm in cyanobacteria , 2011 .

[22]  J. Tyson,et al.  The dynamics of cell cycle regulation. , 2002, BioEssays : news and reviews in molecular, cellular and developmental biology.

[23]  G C Johnston,et al.  Coordination of growth with cell division in the yeast Saccharomyces cerevisiae. , 1977, Experimental cell research.

[24]  J. Bartek,et al.  The retinoblastoma protein pathway and the restriction point. , 1996, Current opinion in cell biology.

[25]  I. Herskowitz,et al.  Signal transduction during pheromone response in yeast. , 1991, Annual review of cell biology.

[26]  L. Hartwell,et al.  Genetic Control of the Cell Division Cycle in Yeast: V. Genetic Analysis of cdc Mutants. , 1973, Genetics.

[27]  H. Kitano.  Systems Biology: A Brief Overview , 2002, Science.

[28]  A. L. Koch,et al.  A model for statistics of the cell division process. , 1962, Journal of general microbiology.

[29]  P. Lord,et al.  Variability in individual cell cycles of Saccharomyces cerevisiae. , 1981, Journal of cell science.

[30]  R. Thomas,et al.  Boolean formalization of genetic control circuits. , 1973, Journal of theoretical biology.

[31]  U. Alon.  An introduction to systems biology : design principles of biological circuits , 2019 .

[32]  R. Storn,et al.  Differential Evolution: A Practical Approach to Global Optimization (Natural Computing Series) , 2005 .

[33]  John J. Tyson,et al.  Optimization and model reduction in the high dimensional parameter space of a budding yeast cell cycle model , 2013, BMC Systems Biology.

[34]  F. Cross,et al.  The effects of molecular noise and size control on variability in the budding yeast cell cycle , 2007, Nature.

[35]  Paolo Ballarini,et al.  Studying Irreversible Transitions in a Model of Cell Cycle Regulation , 2009, PASM@EPEW.

[36]  Luca Cardelli,et al.  Transcriptional Regulation Is a Major Controller of Cell Cycle Transition Dynamics , 2012, PloS one.

[37]  Frederick R. Cross,et al.  Multiple levels of cyclin specificity in cell-cycle control , 2007, Nature Reviews Molecular Cell Biology.

[38]  Attila Csikász-Nagy,et al.  Stochastic Petri Net extension of a yeast cell cycle model. , 2008, Journal of theoretical biology.

[39]  Eric T. Rosenthal,et al.  Cyclin: A protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division , 1983, Cell.

[40]  F. Cross,et al.  Testing a mathematical model of the yeast cell cycle. , 2002, Molecular biology of the cell.

[41]  K Nasmyth,et al.  Viewpoint: Putting the Cell Cycle in Order , 1996, Science.

[42]  L. Hartwell,et al.  Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division , 1977, The Journal of cell biology.

[43]  K. Nasmyth,et al.  Whose end is destruction: cell division and the anaphase-promoting complex. , 1999, Genes & development.

[44]  M. Mendenhall,et al.  An inhibitor of yeast cyclin-dependent protein kinase plays an important role in ensuring the genomic integrity of daughter cells. , 1994, Molecular and cellular biology.

[45]  Attila Csikász-Nagy,et al.  Computational systems biology of the cell cycle , 2009, Briefings Bioinform..

[46]  Steffen Klamt,et al.  SBML qualitative models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools , 2013, BMC Systems Biology.

[47]  P. Sassone-Corsi,et al.  The circadian clock and cell cycle: interconnected biological circuits. , 2013, Current opinion in cell biology.

[48]  Marta Z. Kwiatkowska,et al.  Probabilistic model checking of complex biological pathways , 2008, Theor. Comput. Sci..

[49]  John J. Tyson,et al.  A Stochastic Model Correctly Predicts Changes in Budding Yeast Cell Cycle Dynamics upon Periodic Expression of CLN2 , 2014, PloS one.

[50]  Alida Palmisano.  Coding Biological Systems in a Stochastic Framework - The Case Study of Budding Yeast Cell Cycle , 2010, BIOINFORMATICS.

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

[52]  Katherine C. Chen,et al.  Integrative analysis of cell cycle control in budding yeast. , 2004, Molecular biology of the cell.

[53]  Katherine C. Chen,et al.  Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. , 2003, Current opinion in cell biology.

[54]  B. Novák,et al.  Size control in growing yeast and mammalian cells , 2004, Theoretical Biology and Medical Modelling.

[55]  K. Nasmyth.  At the heart of the budding yeast cell cycle. , 1996, Trends in genetics : TIG.

[56]  David O. Morgan,et al.  The Cell Cycle: Principles of Control , 2014 .

[57]  John J Tyson,et al.  A model of yeast cell-cycle regulation based on multisite phosphorylation , 2010, Molecular systems biology.

[58]  D. Guertin,et al.  Cytokinesis in Eukaryotes , 2002, Microbiology and Molecular Biology Reviews.

[59]  S. Bornholdt,et al.  Boolean Network Model Predicts Cell Cycle Sequence of Fission Yeast , 2007, PloS one.

[60]  Zbigniew Darzynkiewicz,et al.  Analysis of cell cycle by flow cytometry. , 2004, Methods in molecular biology.

[61]  Hiroaki Kitano,et al.  The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models , 2003, Bioinform..

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

[63]  A. Csikász-Nagy,et al.  Circadian rhythms synchronize mitosis in Neurospora crassa , 2014, Proceedings of the National Academy of Sciences.

[64]  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.

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