The continuum model: an experimental and theoretical challenge to the G1 model of cell cycle regulation.

The dominant and current view of cell cycle regulation is that the controls for cell proliferation reside primarily in the Gl phase of the division cycle. This current or classical model is deeply ingrained in cell biology, and has been described very well [ 1, 21; therefore we will only summarize below the basic support of the Gl model. Over the past decade, however, an alternative proposal, the continuum model, has emerged that suggests that there are no Gl-specific events or controls, and that all of the evidence for the importance of the Gl phase can be explained in terms of a continuous process that occurs in all phases of the division cycle [3-71. These early reports addressed previous experimental results and explained them in terms of the continuum model. In a sense, therefore, these analyses were theoretical rather than experimental. The basic ideas of the continuum model are presented in Fig. 1. Recently there has emerged a set of experiments that has been stimulated by the ideas of the continuum model, and these experiments support the basic ideas of the continuum model. This means that the continuum model has been a stimulus to experimental tests, and therefore has an experimental as well as a theoretical base. We will describe these experiments below, and explain how they support the continuum model.