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A quantitative model of the effect of unreplicated DNA on cell cycle progression in frog egg extracts.
Zwolak J
,
Adjerid N
,
Bagci EZ
,
Tyson JJ
,
Sible JC
.
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A critical goal in cell biology is to develop a systems-level perspective of eukaryotic cell cycle controls. Among these controls, a complex signaling network (called 'checkpoints') arrests progression through the cell cycle when there is a threat to genomic integrity such as unreplicated or damaged DNA. Understanding the regulatory principles of cell cycle checkpoints is important because loss of checkpoint regulation may be a requisite step on the roadway to cancer. Mathematical modeling has proved to be a useful guide to cell cycle regulation by revealing the importance of bistability, hysteresis and time lags in governing cell cycle transitions and checkpoint mechanisms. In this report, we propose a mathematical model of the frog egg cell cycle including effects of unreplicated DNA on progression into mitosis. By a stepwise approach utilizing parameter estimation tools, we build a model that is grounded in fundamental behaviors of the cell cycle engine (hysteresis and time lags), includes new elements in the signaling network (Myt1 and Chk1 kinases), and fits a large and diverse body of data from the experimental literature. The model provides a validated framework upon which to build additional aspects of the cell cycle checkpoint signaling network, including those control signals in the mammalian cell cycle that are commonly mutated in cancer.
Bartek,
Chk1 and Chk2 kinases in checkpoint control and cancer.
2003, Pubmed
Bartek,
Chk1 and Chk2 kinases in checkpoint control and cancer.
2003,
Pubmed
Bulavin,
Phosphorylation of Xenopus Cdc25C at Ser285 interferes with ability to activate a DNA damage replication checkpoint in pre-midblastula embryos.
2003,
Pubmed
,
Xenbase
Bulavin,
Dual phosphorylation controls Cdc25 phosphatases and mitotic entry.
2003,
Pubmed
,
Xenbase
Elledge,
Cell cycle checkpoints: preventing an identity crisis.
1996,
Pubmed
Félix,
Triggering of cyclin degradation in interphase extracts of amphibian eggs by cdc2 kinase.
1990,
Pubmed
,
Xenbase
Gautier,
cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
1991,
Pubmed
,
Xenbase
Goldbeter,
A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase.
1991,
Pubmed
Guo,
Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation in response to DNA replication blocks and UV-damaged DNA in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Hanahan,
The hallmarks of cancer.
2000,
Pubmed
Hekmat-Nejad,
Xenopus ATR is a replication-dependent chromatin-binding protein required for the DNA replication checkpoint.
,
Pubmed
,
Xenbase
Hutchins,
Dephosphorylation of the inhibitory phosphorylation site S287 in Xenopus Cdc25C by protein phosphatase-2A is inhibited by 14-3-3 binding.
2002,
Pubmed
,
Xenbase
Izumi,
Elimination of cdc2 phosphorylation sites in the cdc25 phosphatase blocks initiation of M-phase.
1993,
Pubmed
,
Xenbase
Kim,
A maternal form of the phosphatase Cdc25A regulates early embryonic cell cycles in Xenopus laevis.
1999,
Pubmed
,
Xenbase
Kumagai,
14-3-3 proteins act as negative regulators of the mitotic inducer Cdc25 in Xenopus egg 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
Kumagai,
Regulation of the cdc25 protein during the cell cycle in Xenopus extracts.
1992,
Pubmed
,
Xenbase
Kumagai,
The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts.
1998,
Pubmed
,
Xenbase
Kumagai,
The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system.
1991,
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
Lupardus,
A requirement for replication in activation of the ATR-dependent DNA damage checkpoint.
2002,
Pubmed
,
Xenbase
Margolis,
A role for PP1 in the Cdc2/Cyclin B-mediated positive feedback activation of Cdc25.
2006,
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
Novak,
Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte extracts and intact embryos.
1993,
Pubmed
,
Xenbase
Nyberg,
Toward maintaining the genome: DNA damage and replication checkpoints.
2002,
Pubmed
Peter,
In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase.
1990,
Pubmed
Pomerening,
Building a cell cycle oscillator: hysteresis and bistability in the activation of Cdc2.
2003,
Pubmed
,
Xenbase
Qin,
Molecular anatomy of the DNA damage and replication checkpoints.
2003,
Pubmed
Sagata,
Molecular biology. Untangling checkpoints.
2002,
Pubmed
,
Xenbase
Sha,
Hysteresis drives cell-cycle transitions in Xenopus laevis egg extracts.
2003,
Pubmed
,
Xenbase
Shaffer,
Modeling molecular regulatory networks with JigCell and PET.
2009,
Pubmed
,
Xenbase
Shimuta,
Chk1 is activated transiently and targets Cdc25A for degradation at the Xenopus midblastula transition.
2002,
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,
Cyclin activation of p34cdc2.
1990,
Pubmed
,
Xenbase
Yoo,
Adaptation of a DNA replication checkpoint response depends upon inactivation of Claspin by the Polo-like kinase.
2004,
Pubmed
,
Xenbase
Zwolak,
Parameter estimation for a mathematical model of the cell cycle in frog eggs.
2005,
Pubmed
Zwolak,
Globally optimised parameters for a model of mitotic control in frog egg extracts.
2005,
Pubmed
