Robustness of CDK2 in Triggering Cellular Senescence based on Probability of DNA‐damaged Cells Passing G1/S Checkpoint

Recent experiments have shown that cellular senescence, a mechanism employed by cells for thwarting cell proliferation, plays an important role in protecting cells against cancer; therefore, a deeper understanding of cellular senescence can lead to effective cancer treatment. Inhibition of CDK2 is thought to be the critical trigger for cellular senescence. In this study, we first implement a mathematical model of G1/S transition involving the DNA‐damage pathway and show that cellular senescence can be achieved by lowering CDK2. The robustness of CDK2 in triggering cellular senescence is determined from the probability (β) of DNA‐damaged cells passing G1/S checkpoint for normal CDK2 and CDK2‐deficient situations based on different thresholds of the peak time of two important biomarkers, CycE and E2F. The comparison of the values of β under the normal CDK2 and lower CDK2 levels reveals that reducing CDK2 levels can decrease the percentage of damaged cells passing G1/S checkpoint; more importantly, 50% reduc...