FIGURE 4.

Overview of signal transduction in the model network. Shown is temporal evolution of the output of each module at the IR dose of 3 Gy (A) or 5 Gy (B). Upon IR, a number of DSBCs are produced, and ATM and p53 are activated. Consequently, the cell cycle is arrested in the G₁ phase. With repairable DNA damage, only few pulses occur in ATM* and p53* levels before cells recover to normal proliferation, which is driven by activated E2F1. With irreparable DNA damage, ATM* is maintained at high levels after four pulses, whereas p53 level shows pulses in both phases. Activated E2F1 cooperates with p53 to activate caspase 3 and apoptosis ensues.