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J Theor Biol. 1999 Jul 21;199(2):223-33.

Finishing the cell cycle.

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Department of Agricultural Chemical Technology, Technical University of Budapest, Gellért tér 4, Budapest, 1521, Hungary.


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.

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