A quantitative analysis of the kinetics of the G(2) DNA damage checkpoint system.

Abstract:

: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 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 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.

authors

Aguda BD

doi

10.1073/pnas.96.20.11352

keywords:

subject

Has Abstract

pub_date

1999-09-28 00:00:00

pages

11352-7

issue

20

eissn

0027-8424

issn

1091-6490

journal_volume

96

pub_type

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