A quantitative model of the initiation of DNA replication in Saccharomyces cerevisiae predicts the effects of system perturbations

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Requires input from Chen2004(BIOMD0000000056) model but did not work correctly even after integrating both models.

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  • 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.
Submitter of the first revision: Ashley Xavier
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Ashley Xavier, Krishna Kumar Tiwari

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Mathematical Modelling Ontology Ordinary differential equation model

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  • Model originally submitted by : Ashley Xavier
  • Submitted: Dec 5, 2018 3:33:07 PM
  • Last Modified: Jul 13, 2020 1:23:04 PM
  • Version: 3 public model Download this version
    • Submitted on: Jul 13, 2020 1:23:04 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: updated publication details
  • Version: 2 public model Download this version
    • Submitted on: Dec 5, 2018 3:33:07 PM
    • Submitted by: Ashley Xavier
    • With comment: Edited model metadata online.

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