Towards a blueprint of the cell cycle

The understanding of the organisation of cell cycle events is of utmost imp ortance. to devise effective therapeutic strategies for cancer, In this art icle we gather evidences from the literature in support of a system model o f the cell cycle, in which a growth-sensitive threshold controls entry into S phase and the sequential activation of cyclin-dependent kinases, The cyc le is terminated by an End function, that comprises events from the onset o f mitosis to cell division and that may also be modulated by the increase o f cell size, This blueprint allows quantitative predictions by computer sim ulations of steady and transitory states. In fact, we show that the propose d control system applies to budding yeast populations during nutritional sh ift-up and following hyperactivation of the cAMP signalling pathway, Beside s the growth-sensitive control system it is shown to apply to mammalian cel ls both in the exit from quiescence and in active proliferation, The putati ve molecular determinants that set the threshold controlling S phase entry are consistently altered in cancer cells, Finally, we discuss an input/outp ut analysis based on the simulated behaviour derived from the blueprint as a new tool to investigate the road to cancer.