Zhang2007 - Mechanism of DNA damage response (Model1)

  public model
Model Identifier
BIOMD0000001007
Short description
It's a mathematical model depicting the DNA damage response on p53/MDM2 pathway at low and high DNA damage condition. This model represents model schema 1 of the literature.
Format
SBML (L3V1)
Related Publication
  • Exploring mechanisms of the DNA-damage response: p53 pulses and their possible relevance to apoptosis.
  • Zhang T, Brazhnik P, Tyson JJ
  • Cell cycle (Georgetown, Tex.) , 1/ 2007 , Volume 6 , Issue 1 , pages: 85-94 , PubMed ID: 17245126
  • Department of Biological Science, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
  • The transcription factor p53 plays a central role in maintaining genomic integrity. Recent experiments in MCF7 cells have shown that p53 protein level rises and falls in distinct pulses in response to DNA damage. The amplitudes of and intervals between pulses seem to be independent of the extent of damage, and some cells generate regular pulses of p53 over many days. Identifying the molecular mechanisms responsible for such interesting behavior is an important and challenging problem. This paper describes four dual-feedback mechanisms that combine both positive and negative feedback loops, which have been identified in the signaling network responsible for p53 regulation. Mathematical models of all four mechanisms are analyzed to determine if they are consistent with experimental observations and to characterize subtle differences among the possible mechanisms. In addition, a novel molecular mechanism is proposed whereby p53 pulses may induce, at first, cell cycle arrest and, if sustained, cell death. The proposal accounts for basic features of p53-mediated responses to DNA damage and suggests new experiments to probe the dynamics of p53 signaling.
Contributors
Krishna Kumar Tiwari

Metadata information

hasTaxon
Taxonomy Homo sapiens
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
W:0000718
Pathway Ontology DNA damage response pathway
unknownQualifier
Mathematical Modelling Ontology Ordinary differential equation model
isDescribedBy

Curation status
Non-curated


Tags
Name Description Size Actions

Model files

Zhang2007_M1_lowDD.xml SBML L3V1 representation of the Zhang2007 model1 for low DNA damage 55.50 KB Preview | Download

Additional files

Zhang2007_M1_highDD.sedml SEDML file for the Zhang2007 model1 for high DNA damage 23.94 KB Preview | Download
Zhang2007_M1_highDD.xml SBML L3V1 representation of the Zhang2007 model1 for High DNA damage 55.97 KB Preview | Download
Zhang2007_M1_highDD.cps COPASI 4.31(build243) file for the Zhang2007 model1 for high DNA damage 109.54 KB Preview | Download
Zhang2007_M1_lowDD.cps COPASI 4.31(build243) file for the Zhang2007 model1 for low DNA damage 109.53 KB Preview | Download
Zhang2007_M1_lowDD.sedml SEDML file for the Zhang2007 model1 for low DNA damage 23.93 KB Preview | Download
Model1-One.ode Model file provided by authors 855.00 Bytes Preview | Download

  • Model originally submitted by : Krishna Kumar Tiwari
  • Submitted: 26-May-2021 12:16:26
  • Last Modified: 26-May-2021 13:00:24
Revisions
  • Version: 3 public model Download this version
    • Submitted on: 26-May-2021 13:00:24
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Updated model file provided by authors
  • Version: 2 public model Download this version
    • Submitted on: 26-May-2021 12:16:26
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Automatically added model identifier BIOMD0000001007

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

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: Variable used inside SBML models


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Curator's comment:
(added: 26 May 2021, 12:15:37, updated: 26 May 2021, 12:59:01)
Reproduced literature figure1, Row1 (model1) results. Model encoded and simulated copasi 4.31(Build234). CPS, SBML and SEDML file for both low (2) and high (6) DNA damage are given as attachment under model files. Some IC are different from published paper which was agreed upon by authors.