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MODEL1607210001 - Barr2017 - Dynamics of p21 in hTert-RPE1 cells

 

The following model is part of the non-curated branch of BioModels Database. While the syntax of the model has been verified, its semantics remains unchecked. Any annotation present in the models is not a product of BioModels' annotators. We are doing our best to incorporate this model into the curated branch as soon as possible. In the meantime, we display only limited metadata here. For further information about the model, please download the SBML file.


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Reference Publication
Publication ID: 10.1038/ncomms14728...
Alexis R. Barr, Samuel Cooper, Frank S. Heldt, Francesca Butera, Henriette Stoy, Jörg Mansfeld, Béla Novák & Chris Bakal
DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression
Nature Communications
1 Division of Cancer Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK. 2 Department of Computational Systems Medicine, Imperial College, South Kensington Campus, London SW7 2AZ, UK. 3 Department of Biochemistry, OCISB, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. 4 Cell Cycle, Biotechnology Centre, TU Dresden, 01307 Dresden, Germany.  [more]
Model
Original Model: MODEL1607210001.origin
Submitter: Frank Stefan Heldt
Submission Date: 21 Jul 2016 08:15:17 UTC
Last Modification Date: 20 Mar 2017 13:17:56 UTC
Creation Date: 09 Jun 2016 17:37:08 UTC
Encoders:  Frank Stefan Heldt
 
Notes
Barr2017 - Dynamics of p21 in hTert-RPE1 cells

This model is described in the article:

Alexis R. Barr, Samuel Cooper, Frank S. Heldt, Francesca Butera, Henriette Stoy, Jörg Mansfeld, Béla Novák & Chris Bakal
Nature Communications

Abstract:

Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. However, the role of p21 in maintaining genomic stability in the absence of exogenous DNA-damaging agents is unclear. Here, using live single-cell measurements of p21 protein in proliferating cultures, we show that naturally occurring DNA damage incurred over S-phase causes p53-dependent accumulation of p21 during mother G2- and daughter G1-phases. High p21 levels mediate G1 arrest via CDK inhibition, yet lower levels have no impact on G1 progression, and the ubiquitin ligases CRL4Cdt2 and SCFSkp2 couple to degrade p21 prior to the G1/S transition. Mathematical modelling reveals that a bistable switch, created by CRL4Cdt2, promotes irreversible S-phase entry by keeping p21 levels low, preventing premature S-phase exit upon DNA damage. Thus, we characterize how p21 regulates the proliferation-quiescence decision to maintain genomic stability.

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.

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