K. Iwamoto, Y. Tashima, H. Hamada, M. Okamoto, and Y. Eguchi (Japan)
G1/S checkpoint, restriction point, late G1 phase, DNA damage, G1 arrest, mathematical model
The transition from G1 phase to S phase in the cell cy cle is regulated by G1/S checkpoint, which can arrest the G1 progression when DNA-damage occurred. How ever, it was reported that G1 arrest was not induced when DNA-damage occurred at late G1 phase. This finding im plies that G1/S checkpoint cannot detect the DNA-damage on late G1 phase. The inadequate regulation of G1/S checkpoint to cell cycle progression produces serious ef fects on both the cellular homeostasis and genetic sta bility. In this paper, to verify the inadequate regulation of G1/S checkpoint, we constructed a novel mathemati cal model (proposed model), which integrated G1/S check point with p53-dependent DNA-damage pathway, and sim ulated a dynamic behavior of G1/S transition involving DNA-damage. The hot issue of the study is that the sim ulation results of the proposed model with/without DNA damage can qualitatively realize the biological findings such that G1/S checkpoint cannot detect the DNA-damage on late G1 phase.
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