Fig. 5.

The eukaryote cell cycle as a bistable oscillator. The central logic of a typical binary fission cell cycle is that the cell can switch suddenly between two metastable states, one (G1) with low and one (S + M) with high cyclin-dependent kinase activity. The master controlling switch activates the anaphase-promoting complex (APC) that uses ubiquitin/proteasome-mediated proteolysis to digest the cohesins that bind sister chromatids together and reset the cell cycle by digesting cyclins and many other proteins. This sudden proteolytic destruction of cyclin-dependent kinase causes a precipitous drop in its activity (downward pointing arrow). As the cell grows the ratio of cyclins to their inhibitors increases gradually so eventually there is enough active cyclin to stimulate its associated kinase to initiate a burst of phosphorylations of numerous proteins critical to the G1/S-phase transition (called START in budding yeast, although the beginning of the cycle is more logically the onset of synthesis of origin recognition complexes, cyclins and their inhibitors immediately following the massive proteolysis that initiates anaphase). The upward pointing arrow represents this sudden activation of cyclin-dependent kinase without significant change in cyclin concentration, which typically occurs at a particular cell size effectively set by the rate of cyclin accumulation. Note that it is the ratio of cyclin to APC (abscissa) that is the master controller, not the absolute level of cyclin. START involves the initiation of DNA replication and of centriole duplication: like chromatin centrioles exist in two states, duplicatable and non-duplicatable. The centrosome and centriole evolved at the same time as the nucleus and their duplication cycles have been coupled ever since (Wong and Stearns, 2003); many organisms that lost cilia have also lost centrioles (e.g. higher plants and fungi) and are thus degenerate compared with animals and most protozoa. A second set of cyclin-dependent processes (not shown) is triggered after replication is complete to initiate chromosome condensation and spindle assembly.