Figure 3

Diagram of the cell cycle model. In this discrete model, cells progress through a cell cycle comprising three phases: G ₁ , S, and G ₂ M. At the end of the G ₂ M phase, cells divide and new cells begin their cycle in G ₁ . At the last stage of phase G ₁ , we modelled the restriction point R, where DNA integrity and external conditions (overpopulation and hypoxia) are checked. If overpopulation occurs, APC is activated; if hypoxia occurs, SMAD is activated. Both these conditions lead cells to G ₀ (quiescence). Cells remain in the quiescent phase in the absence of external changes, otherwise they may return to the proliferative cycle (at the first step of S phase). DNA damage can also activate the p53 pathway, which leads cells to the apoptotic phase. Cells at the end of the apoptotic phase die and disappear from the computational domain.