Systems-level feedback in cell-cycle control.

Alternation of chromosome replication and segregation is essential for successful completion of the cell cycle and it requires an oscillation of Cdk1 (cyclin-dependent kinase 1)-CycB (cyclin B) activity. In the present review, we illustrate the essential features of checkpoint controlled and uncontrolled cell-cycle oscillations by using mechanical metaphors. Despite variations in the molecular details of the oscillatory mechanism, the underlying network motifs responsible for the oscillations are always well-conserved. The checkpoint-controlled cell cycles are always driven by a negative-feedback loop amplified by double-negative feedbacks (antagonism).

[1]  K Nasmyth,et al.  Control of cyclin ubiquitination by CDK-regulated binding of Hct1 to the anaphase promoting complex. , 1998, Science.

[2]  M. Crosby,et al.  Cell Cycle: Principles of Control , 2007, The Yale Journal of Biology and Medicine.

[3]  David P. Toczyski,et al.  Securin and B-cyclin/CDK are the only essential targets of the APC , 2003, Nature Cell Biology.

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

[5]  F. M. Yeong,et al.  Exit from mitosis in budding yeast: biphasic inactivation of the Cdc28-Clb2 mitotic kinase and the role of Cdc20. , 2000, Molecular cell.

[6]  M. Kirschner,et al.  A 20s complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B , 1995, Cell.

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

[8]  J. Diffley,et al.  Two steps in the assembly of complexes at yeast replication origins in vivo , 1994, Cell.

[9]  Kim Nasmyth,et al.  The Polo‐like kinase Cdc5p and the WD‐repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae , 1998, The EMBO journal.

[10]  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.

[11]  F. Cross,et al.  Mitotic exit in the absence of separase activity. , 2009, Molecular biology of the cell.

[12]  E. Salmon,et al.  The spindle-assembly checkpoint in space and time , 2007, Nature Reviews Molecular Cell Biology.

[13]  J. Tyson,et al.  Design principles of biochemical oscillators , 2008, Nature Reviews Molecular Cell Biology.

[14]  J. Tyson,et al.  Regulation of the eukaryotic cell cycle: molecular antagonism, hysteresis, and irreversible transitions. , 2001, Journal of theoretical biology.

[15]  Kim Nasmyth,et al.  The B-type cyclin kinase inhibitor p40 SIC1 controls the G1 to S transition in S. cerevisiae , 1994, Cell.

[16]  David O. Morgan,et al.  The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae , 1998, Current Biology.

[17]  Uttam Surana,et al.  The role of phosphorylation and the CDC28 protein kinase in cell cycle-regulated nuclear import of the S. cerevisiae transcription factor SW15 , 1991, Cell.

[18]  J. Blow,et al.  A role for the nuclear envelope in controlling DNA replication within the cell cycle , 1988, Nature.

[19]  Michael S. Cohen,et al.  APC/C-Cdh1-mediated degradation of the Polo kinase Cdc5 promotes the return of Cdc14 into the nucleolus. , 2008, Genes & Development.

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

[21]  Steven P. Gygi,et al.  Cdc28-Dependent Regulation of the Cdc5/Polo Kinase , 2005, Current Biology.

[22]  John J Tyson,et al.  A model for restriction point control of the mammalian cell cycle. , 2004, Journal of theoretical biology.

[23]  J. Tyson,et al.  Checkpoints in the cell cycle from a modeler's perspective. , 1995, Progress in cell cycle research.

[24]  John J. Tyson,et al.  Temporal Organization of the Cell Cycle , 2008, Current Biology.

[25]  Friedrich Lottspeich,et al.  Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1 , 1999, Nature.

[26]  Mike Tyers,et al.  Mechanisms that help the yeast cell cycle clock tick: G2 cyclins transcriptionally activate G2 cyclins and repress G1 cyclins , 1993, Cell.

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

[28]  J. Tyson,et al.  Model scenarios for evolution of the eukaryotic cell cycle. , 1998, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[29]  S. Carr,et al.  Phosphorylation of Sic1p by G1 Cdk required for its degradation and entry into S phase. , 1997, Science.

[30]  K Nasmyth,et al.  The transcription factor Swi5 regulates expression of the cyclin kinase inhibitor p40SIC1 , 1996, Molecular and cellular biology.

[31]  Steven A. Carr,et al.  Phosphorylation by Cyclin B-Cdk Underlies Release of Mitotic Exit Activator Cdc14 from the Nucleolus , 2004, Science.

[32]  K Nasmyth,et al.  Evolution of the cell cycle. , 1995, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[33]  L. Dirick,et al.  Roles and regulation of Cln‐Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae. , 1995, The EMBO journal.

[34]  A. Hershko,et al.  The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. , 1995, Molecular biology of the cell.

[35]  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.

[36]  J. Tyson,et al.  Mathematical model of the cell division cycle of fission yeast. , 2001, Chaos.

[37]  Angelika Amon,et al.  Separase, Polo Kinase, the Kinetochore Protein Slk19, and Spo12 Function in a Network that Controls Cdc14 Localization during Early Anaphase , 2002, Cell.

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

[39]  Karl Mechtler,et al.  Phosphorylation of the Cohesin Subunit Scc1 by Polo/Cdc5 Kinase Regulates Sister Chromatid Separation in Yeast , 2001, Cell.

[40]  Béla Novák,et al.  Supplementary Fig. 1 , 2021 .

[41]  A. Murray,et al.  Dominoes and clocks: the union of two views of the cell cycle. , 1989, Science.

[42]  U. Surana,et al.  Cdc20 is essential for the cyclosome-mediated proteolysis of both Pds1 and Clb2 during M phase in budding yeast , 1998, Current Biology.

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

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

[45]  Eric Karsenti,et al.  Triggering of cyclin degradation in interphase extracts of amphibian eggs by cdc2 kinase , 1990, Nature.

[46]  K Nasmyth,et al.  Splitting the chromosome: cutting the ties that bind sister chromatids. , 2000, Novartis Foundation symposium.

[47]  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.

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

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

[50]  S. Moreno,et al.  Regulation of progression through the G1 phase of the cell cycle by the rum1+ gene , 1994 .