Mathematical modelling of whole chromosome replication

de Moura, Alessandro P.S., Retkute, Renata, Hawkins, Michelle and Nieduszynski, Conrad A. ORCID: (2010) Mathematical modelling of whole chromosome replication. Nucleic Acids Research, 38 (17). pp. 5623-5633. ISSN 0305-1048

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All chromosomes must be completely replicated prior to cell division, a requirement that demands the activation of a sufficient number of appropriately distributed DNA replication origins. Here we investigate how the activity of multiple origins on each chromosome is coordinated to ensure successful replication. We present a stochastic model for whole chromosome replication where the dynamics are based upon the parameters of individual origins. Using this model we demonstrate that mean replication time at any given chromosome position is determined collectively by the parameters of all origins. Combining parameter estimation with extensive simulations we show that there is a range of model parameters consistent with mean replication data, emphasising the need for caution in interpreting such data. In contrast, the replicated-fraction at time points through S phase contains more information than mean replication time data and allowed us to use our model to uniquely estimate many origin parameters. These estimated parameters enable us to make a number of predictions that showed agreement with independent experimental data, confirming that our model has predictive power. In summary, we demonstrate that a stochastic model can recapitulate experimental observations, including those that might be interpreted as deterministic such as ordered origin activation times.

Item Type: Article
Additional Information: Funding Information: The Leverhulme Trust; The University of Nottingham; The University of Aberdeen; and the Biotechnology and Biological Sciences Research Council (grant numbers BB/ E023754/1, BB/G001596/1); CAN is a David Phillips Fellow. Funding for open access charge: Biotechnology and Biological Sciences Research Council.
Uncontrolled Keywords: genetics ,/dk/atira/pure/subjectarea/asjc/1300/1311
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 08 Sep 2022 08:30
Last Modified: 20 Oct 2022 18:31
DOI: 10.1093/nar/gkq343

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