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

被引：69
作者：
Aguda, BD [1 ]
机构：
[1] Laurentian Univ, Dept Chem & Biochem, Sudbury, ON P3E 2C6, Canada
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1999年 / 96卷 / 20期
关键词：
D O I：
10.1073/pnas.96.20.11352
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
A detailed model of the G(2) 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 ho cv 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 14-3-3-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 G(2) arrest.
引用
收藏
页码：11352 / 11357
页数：6
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