Fig. 1. G2/M DNA damage checkpoint regulatory network.

The G2/M DNA damage biopathway for the reaction network of key proteins is converted into a mathematical structure based on ODEs involving the law of mass conservations and a hybrid framework combining mass action and Michaelis-Menten kinetics. Each factor, as defined in the text and Supplementary information, is identified by a unique color. Gene symbols have been used to be consistent with our previous model of the mitotic cell cycle regulation⁹. Here, S1 denotes active MPF kinase (CCNB:CDK1), S2 denotes active PLK1 kinase (phosphorylated), S3 denotes activation of ATM or ATR-induced DNA damage response, and S4 denotes activities of the E3 ubiquitin ligase, MDM2. PPase represents generic phosphatases. The model consists of 34 ODEs governing 22 interaction reactions (k_fn denotes the forward rate constant and k_rn denotes the reverse rate constant for reaction n) of 50 key mitotic and DNA damage checkpoint regulation proteins and associated protein complexes and includes 15 synthesis reactions (k_s: synthesis rate constant) and 26 reactions of multiple degradations (k_dn: self-degradation rate constant, k_dn.n: degradation rate constant by other factors including APP/CP:CDC20 and APC/CT:CDH1). Synthesis k_s represents either expression of a protein factor or accumulation of a specific post translationally modified factor. The crosstalk components in TP53 and PLK1 pathways are highlighted using background shadows.