Cell Cycle Commitment and the Origins of Cell Cycle Variability

Exit of cells from quiescence following mitogenic stimulation is highly asynchronous, and there a great deal heterogeneity in the response. Even single, clonal population, some re-enter cell cycle after sub-optimal signal while other, seemingly identical cells, do not, though they remain capable responding to higher level stimulus. This review will consider origins this variability heterogeneity, both re-entering context commitment decisions continuously cycling populations. Particular attention be paid role two interacting molecular networks, namely RB-E2F APC/C CDH1 “switches.” These networks have property bistability it seems likely that are responsible for dynamic behavior previously described kinetically by Transition Probability models cycle. The relationship between these switches so-called Restriction Point also considered.