Control models of cell cycle transit, exit, and arrest

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Abstract
Several distinct cycles mediate the events which occur between one cell division and the next. In micro-organisms there are generally two cycles. One governs biomass growth, the other DNA synthesis and cell division. In higher eukaryotes there can be as many as four distinct cycles, with growth, DNA synthesis, cell division, and nuclear division each possessing its own functional sequence of events. These cycles are controlled and coordinated by several different regulatory mechanisms. Restriction points are specific steps in the cycle whose completion is governed by external regulatory agents. One set of restriction points requires nutrients and growth hormones for step completion. Another set serves as receptors for differentiating factors which cause cycle arrest and initiate cellular differentiation. There is currently a debate as to whether restriction point inhibition involves permanent arrest or temporary arrest with a stochastic arrested-state residence time controlled by a transition probability mechanism. Tissue sizing is a process of negative feedback inhibition mediated by intercellular communication via cell surface contact and the extracellular matrix. Sizers commonly operate throughout broad portions of the cycle and appear to cause a slowing of cycle transit velocity rather than arrest. Sizers are probably the major regulatory mechanism for cell growth under conditions of nutrient and growth factor excess. They also generate compensatory proliferation following wounding or cell death. A growing body of evidence suggests that both the transit velocity, with which cells move through their several cycles, and the coordination of the cycles are controlled by intracellular regulatory mechanisms which behave as biological oscillators. These oscillators trigger complex sequences of events such as DNA synthesis and cell division.

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