A mathematical study of the robustness of G2/M regulatory network in response to DNA damage with parameters sensitivity

A mathematical analysis of G2/M regulatory network is carried out by performing a study of the robustness of biological systems with kinetic parameters sensitivity. Numerical experiments are performed to investigate local sensitivity to identified significant kinetic parameters relevant to key proteins involved in G2/M phase transition. A global sensitivity analysis is performed to reveal the relationship between the probability of a DNA-damaged cell passing through as a healthy cell and the initial perturbation of parameters in the G2/M model. Using statistical hypothesis testing with the Type II error, this enables prediction of robustness of cell cycle to DNA damage signal when the global perturbation of G2/M regulatory network is small enough. It is found that the robustness of G2/M network declines as the level of the DNA damage rises. The aforementioned findings are inconsistent with existing experimental observations. © 2014 Elsevier Inc. All rights reserved.