Finishing the cell cycle.
The eukaryotic cell division cycle consists of two characteristic states: G1, when replication origins of chromosomes are in a pre-replicative state, and S/G2/M, when they are in a post-replicative state (Nasmyth, 1995). Using straightforward biochemical kinetics, we show that these two states can be created by antagonistic interactions between cyclin-dependent kinases (Cdk) and their foes: the cyclin-degradation machinery (APC) and a stoichiometric inhibitor (CKI). Irreversible transitions between these two self-maintaining steady states drive progress through the cell cycle: at "Start" a cell leaves the G1 state and commences chromosome replication, and at "Finish" the cell separates the products of replication to the incipient daughter cells and re-enters G1. We propose that a protein-phosphatase, by up-regulating the APC and by stabilizing the CKI, plays an essential role at Finish. The phosphatase acts in parallel pathways; hence, cells can leave mitosis in the absence of cyclin degradation or in the absence of the CKI.
Department of Agricultural Chemical Technology, Technical University of Budapest, Gellért tér 4, Budapest, 1521, Hungary. bnovak@chem.bme.hu
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Novák
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Tóth
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Csikász-Nagy
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Györffy
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Tyson
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Nasmyth
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D003198:Computer Simulation; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology*; D005057:Eukaryotic Cells / Q000166:cytology*; D008954:Models, Biological
D018844:Cyclin-Dependent Kinases