Mathematical modelling of whole chromosome replication

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

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Official URL: http://nar.oxfordjournals.org/content/38/17/5623.full

Abstract

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
Schools/Departments:Faculty of Medicine and Health Sciences > School of Biology
ID Code:1370
Deposited By:Nieduszynski, Dr Conrad A
Deposited On:12 Oct 2010 15:06
Last Modified:12 Oct 2010 15:06

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