Gidvani2012 - DNA replication initiation model in S. Cevevisiae

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Model Identifier
MODEL2003180001
Short description
A quantitative model of the initiation of DNA replication in Saccharomyces cerevisiae predicts the effects of system perturbations. Model is encoded by Matthew Maire and submitted in BioModels by Krishna Kumar Tiwari.
Format
SBML (L2V4)
Related Publication
  • A quantitative model of the initiation of DNA replication in Saccharomyces cerevisiae predicts the effects of system perturbations.
  • Ingalls BP, Sudmant P, Ingalls BP, Ingalls BP, Ingalls BP, Duncker BP, Ingalls BP
  • BMC systems biology , 6/ 2012 , Volume 6 , pages: 78 , PubMed ID: 22738223
  • Department of Biology, University of Waterloo, Waterloo, ON, Canada.
  • Eukaryotic cell proliferation involves DNA replication, a tightly regulated process mediated by a multitude of protein factors. In budding yeast, the initiation of replication is facilitated by the heterohexameric origin recognition complex (ORC). ORC binds to specific origins of replication and then serves as a scaffold for the recruitment of other factors such as Cdt1, Cdc6, the Mcm2-7 complex, Cdc45 and the Dbf4-Cdc7 kinase complex. While many of the mechanisms controlling these associations are well documented, mathematical models are needed to explore the network's dynamic behaviour. We have developed an ordinary differential equation-based model of the protein-protein interaction network describing replication initiation.The model was validated against quantified levels of protein factors over a range of cell cycle timepoints. Using chromatin extracts from synchronized Saccharomyces cerevisiae cell cultures, we were able to monitor the in vivo fluctuations of several of the aforementioned proteins, with additional data obtained from the literature. The model behaviour conforms to perturbation trials previously reported in the literature, and accurately predicts the results of our own knockdown experiments. Furthermore, we successfully incorporated our replication initiation model into an established model of the entire yeast cell cycle, thus providing a comprehensive description of these processes.This study establishes a robust model of the processes driving DNA replication initiation. The model was validated against observed cell concentrations of the driving factors, and characterizes the interactions between factors implicated in eukaryotic DNA replication. Finally, this model can serve as a guide in efforts to generate a comprehensive model of the mammalian cell cycle in order to explore cancer-related phenotypes.
Contributors
Submitter of the first revision: Krishna Kumar Tiwari
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Krishna Kumar Tiwari

Metadata information

isDescribedBy (1 statement)
PubMed 22738223

hasTaxon (1 statement)
hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Non-curated
Modelling approach(es)
ordinary differential equation model
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Model files
gidvani2012.xml SBML L2V4 file for the model 76.28 KB Preview | Download

Additional files
gidvani2012.cps COPASI 4.24(Built217) file for the model 125.93 KB Preview | Download
gidvani2012.sedml SEDML file for the model 1.01 KB Preview | Download

  • Model originally submitted by : Krishna Kumar Tiwari
  • Submitted: Mar 18, 2020 2:52:27 PM
  • Last Modified: May 6, 2020 11:09:59 AM
Revisions
  • Version: 4 public model Download this version
    • Submitted on: May 6, 2020 11:09:59 AM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Edited model metadata online.
  • Version: 2 public model Download this version
    • Submitted on: Mar 18, 2020 2:52:27 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Edited model metadata online.

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