Mathematical modeling and sensitivity analysis of G1/S phase in the cell cycle including the DNA-damage signal transduction pathway.
The cell cycle has checkpoint systems, which control G1/S, G2/M and G0/G1 phase transitions. When a normal cell suffers from DNA-damage, the signal transduction of DNA-damage causes the cell cycle arrest by using the checkpoint systems. Therefore, the elucidation of interaction between the signal transduction of DNA-damage and the checkpoint systems is an important problem. In this study, we constructed a novel mathematical model (proposed model) which integrated G1/S-checkpoint model with a signal transduction of DNA damage model and performed some numerical simulations. The proposed model realized some biological findings of G1/S phase with or without DNA-damage, which suggested that proposed model is biologically appropriate. Moreover, the results of sensitivity analysis of the proposed model indicated the predominant factors of G1/S phase and some factors concerned with the transformation of cells.
Iwamoto
Kazunari
K
Laboratory for Bioinformatics, Graduate School of Systems Life Sciences, Kyushu University, Higashiku, Fukuoka, Japan.
Tashima
Yoshihiko
Y
Hamada
Hiroyuki
H
Eguchi
Yukihiro
Y
Okamoto
Masahiro
M
D003198:Computer Simulation; D004249:DNA Damage; D016193:G1 Phase / Q000502:physiology*; D008954:Models, Biological; D016196:S Phase / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics*