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Nucleic Acids Res. 2010 Sep;38(17):5623-33. doi: 10.1093/nar/gkq343. Epub 2010 May 10.

Mathematical modelling of whole chromosome replication.

Author information

1
Department of Physics, University of Aberdeen, Aberdeen AB24 3UE and School of Biology, University of Nottingham, Nottingham NG7 2UH, UK.

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.

PMID:
20457753
PMCID:
PMC2943597
DOI:
10.1093/nar/gkq343
[Indexed for MEDLINE]
Free PMC Article

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