Barr2016 - All-or-nothing G1/S transition

Barr2016 - All-or-nothing G1/S
transition

This model is described in the article:

A Dynamical Framework for
the All-or-None G1/S Transition.

Barr AR, Heldt FS, Zhang T, Bakal C,
Novák B.
Cell Syst 2016 Jan; 2(1): 27-37
Abstract:

The transition from G1 into DNA replication (S phase) is an
emergent behavior resulting from dynamic and complex
interactions between cyclin-dependent kinases (Cdks), Cdk
inhibitors (CKIs), and the anaphase-promoting complex/cyclosome
(APC/C). Understanding the cellular decision to commit to
S phase requires a quantitative description of these
interactions. We apply quantitative imaging of single human
cells to track the expression of G1/S regulators and use these
data to parametrize a stochastic mathematical model of the G1/S
transition. We show that a rapid, proteolytic, double-negative
feedback loop between Cdk2:Cyclin and the Cdk inhibitor
p27(Kip1) drives a switch-like entry into S phase. Furthermore,
our model predicts that increasing Emi1 levels throughout S
phase are critical in maintaining irreversibility of the G1/S
transition, which we validate using Emi1 knockdown and live
imaging of G1/S reporters. This work provides insight into the
general design principles of the signaling networks governing
the temporally abrupt transitions between cell-cycle
phases.

This model is hosted on
BioModels Database
and identified by:
BIOMD0000000646.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.

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