A quantitative analysis of the kinetics of the G2 DNA damage checkpoint system

Model Status

This CellML version of the models runs in PCEnv to reproduce the results shown in figure 8 of the published paper. Units have been checked and are consistent.

Model Structure

ABSTRACT: A detailed model of the G2 DNA damage checkpoint (G2DDC) system is presented that includes complex regulatory networks of the mitotic kinase Cdc2, phosphatase Cdc25, Wee1 kinase, and damage signal transduction pathways involving Chk1 and p53. Assumptions on the kinetic equations of the G2DDC are made, and computer simulations are carried out to demonstrate how the various subsystems operate to delay or arrest cell cycle progression. The detailed model could be used to explain various experiments relevant to G2DDC reported recently, including the nuclear export of 1433 bound Cdc25, the down-regulation of cyclin B1 expression by p53, the effect of Chk1 and p53 on Cdc25 levels, and Wee1 degradation. It also is shown that, under certain conditions, p53 is necessary to sustain a G2 arrest.

The complete original paper reference is cited below:

A quantitative analysis of the kinetics of the G2 DNA damage checkpoint system, Baltazar D. Aguda, 1999 Proceedings of the National Academy of Sciences, 96, 11352-11357 PubMed ID: 10500180

Schematic diagram of the G2DDC system showing the subsystems involving Wee1, MPF, Cdc25, and signal transduction pathways.

The MPF subsystem.

The Cdc25 subsystem.

The Wee1 subsystem.