Barr2016 - All-or-nothing G1/S transition

ABSTRACT: 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. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Emma Fairbanks  

PROVIDER: BIOMD0000000646 | BioModels | 2024-09-02

REPOSITORIES: BioModels