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Proc Natl Acad Sci U S A
2003 Feb 04;1003:975-80. doi: 10.1073/pnas.0235349100.
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Hysteresis drives cell-cycle transitions in Xenopus laevis egg extracts.
Sha W, Moore J, Chen K, Lassaletta AD, Yi CS, Tyson JJ, Sible JC.
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Cells progressing through the cell cycle must commit irreversibly to mitosis without slipping back to interphase before properly segregating their chromosomes. A mathematical model of cell-cycle progression in cell-free egg extracts from frog predicts that irreversible transitions into and out of mitosis are driven by hysteresis in the molecular control system. Hysteresis refers to toggle-like switching behavior in a dynamical system. In the mathematical model, the toggle switch is created by positive feedback in the phosphorylation reactions controlling the activity of Cdc2, a protein kinase bound to its regulatory subunit, cyclin B. To determine whether hysteresis underlies entry into and exit from mitosis in cell-free egg extracts, we tested three predictions of the Novak-Tyson model. (i) The minimal concentration of cyclin B necessary to drive an interphase extract into mitosis is distinctly higher than the minimal concentration necessary to hold a mitotic extract in mitosis, evidence for hysteresis. (ii) Unreplicated DNA elevates the cyclin threshold for Cdc2 activation, indication that checkpoints operate by enlarging the hysteresis loop. (iii) A dramatic "slowing down" in the rate of Cdc2 activation is detected at concentrations of cyclin B marginally above the activation threshold. All three predictions were validated. These observations confirm hysteresis as the driving force for cell-cycle transitions into and out of mitosis.
Aguda,
A quantitative analysis of the kinetics of the G(2) DNA damage checkpoint system.
1999, Pubmed
Aguda,
A quantitative analysis of the kinetics of the G(2) DNA damage checkpoint system.
1999,
Pubmed Clarke,
Cyclin A- and cyclin B-dependent protein kinases are regulated by different mechanisms in Xenopus egg extracts.
1992,
Pubmed
,
Xenbase Cross,
Testing a mathematical model of the yeast cell cycle.
2002,
Pubmed Dasso,
Completion of DNA replication is monitored by a feedback system that controls the initiation of mitosis in vitro: studies in Xenopus.
1990,
Pubmed
,
Xenbase Evans,
Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division.
1983,
Pubmed Félix,
Triggering of cyclin degradation in interphase extracts of amphibian eggs by cdc2 kinase.
1990,
Pubmed
,
Xenbase Ferrell,
The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes.
1998,
Pubmed
,
Xenbase Ferrell,
Bistability in cell signaling: How to make continuous processes discontinuous, and reversible processes irreversible.
2001,
Pubmed
,
Xenbase Gautier,
cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
1991,
Pubmed
,
Xenbase Gautier,
Cyclin is a component of maturation-promoting factor from Xenopus.
1990,
Pubmed
,
Xenbase Goldbeter,
A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase.
1991,
Pubmed Hartley,
A role for cyclin E/Cdk2 in the timing of the midblastula transition in Xenopus embryos.
1997,
Pubmed
,
Xenbase Holloway,
Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor.
1993,
Pubmed
,
Xenbase Izumi,
Elimination of cdc2 phosphorylation sites in the cdc25 phosphatase blocks initiation of M-phase.
1993,
Pubmed
,
Xenbase Kappas,
Dissection of the XChk1 signaling pathway in Xenopus laevis embryos.
2000,
Pubmed
,
Xenbase Kim,
A maternal form of the phosphatase Cdc25A regulates early embryonic cell cycles in Xenopus laevis.
1999,
Pubmed
,
Xenbase Kumagai,
Regulation of the cdc25 protein during the cell cycle in Xenopus extracts.
1992,
Pubmed
,
Xenbase Kumagai,
The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system.
1991,
Pubmed
,
Xenbase Kumagai,
The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts.
1998,
Pubmed
,
Xenbase Kumagai,
Control of the Cdc2/cyclin B complex in Xenopus egg extracts arrested at a G2/M checkpoint with DNA synthesis inhibitors.
1995,
Pubmed
,
Xenbase Lee,
Positive regulation of Wee1 by Chk1 and 14-3-3 proteins.
2001,
Pubmed
,
Xenbase Lorca,
Fizzy is required for activation of the APC/cyclosome in Xenopus egg extracts.
1998,
Pubmed
,
Xenbase Marlovits,
Modeling M-phase control in Xenopus oocyte extracts: the surveillance mechanism for unreplicated DNA.
1998,
Pubmed
,
Xenbase Mueller,
Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15.
1995,
Pubmed
,
Xenbase Mueller,
Cell cycle regulation of a Xenopus Wee1-like kinase.
1995,
Pubmed
,
Xenbase Murray,
Cell cycle extracts.
1991,
Pubmed Murray,
The role of cyclin synthesis and degradation in the control of maturation promoting factor activity.
1989,
Pubmed
,
Xenbase Murray,
Cyclin synthesis drives the early embryonic cell cycle.
1989,
Pubmed
,
Xenbase Nasmyth,
At the heart of the budding yeast cell cycle.
1996,
Pubmed Novak,
Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte extracts and intact embryos.
1993,
Pubmed
,
Xenbase Smythe,
Coupling of mitosis to the completion of S phase in Xenopus occurs via modulation of the tyrosine kinase that phosphorylates p34cdc2.
1992,
Pubmed
,
Xenbase Solomon,
Hysteresis meets the cell cycle.
2003,
Pubmed
,
Xenbase Solomon,
Cyclin activation of p34cdc2.
1990,
Pubmed
,
Xenbase Stemmann,
Dual inhibition of sister chromatid separation at metaphase.
2001,
Pubmed
,
Xenbase Thron,
Bistable biochemical switching and the control of the events of the cell cycle.
1997,
Pubmed Tyson,
Chemical kinetic theory: understanding cell-cycle regulation.
1996,
Pubmed Tyson,
Modeling the cell division cycle: cdc2 and cyclin interactions.
1991,
Pubmed Tyson,
Regulation of the eukaryotic cell cycle: molecular antagonism, hysteresis, and irreversible transitions.
2001,
Pubmed
