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A model for the spatiotemporal organization of DNA replication in Saccharomyces cerevisiae

Spiesser, T.W., Klipp, E. and Barberis, Matteo (2009) A model for the spatiotemporal organization of DNA replication in Saccharomyces cerevisiae Molecular Genetics and Genomics, 282 (1). pp. 25-35.

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DNA replication in eukaryotes is considered to proceed according to a precise program in which each chromosomal region is duplicated in a defined temporal order. However, recent studies reveal an intrinsic temporal disorder in the replication of yeast chromosome VI. Here we provide a model of the chromosomal duplication to study the temporal sequence of origin activation in budding yeast. The model comprises four parameters that influence the DNA replication system: the lengths of the chromosomes, the explicit chromosomal positions for all replication origins as well as their distinct initiation times and the replication fork migration rate. The designed model is able to reproduce the available experimental data in form of replication profiles. The dynamics of DNA replication was monitored during simulations of wild type and randomly perturbed replication conditions. Severe loss of origin function showed only little influence on the replication dynamics, so systematic deletions of origins (or loss of efficiency) were simulated to provide predictions to be tested experimentally. The simulations provide new insights into the complex system of DNA replication, showing that the system is robust to perturbation, and giving hints about the influence of a possible disordered firing.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Spiesser, T.W.
Klipp, E.
Date : 22 March 2009
Funders : European Commission
DOI : 10.1007/s00438-009-0443-9
Grant Title : Project ENFIN
Copyright Disclaimer : © The Author(s) 2009. This article is published with open access at . This article is published under an open access license. Please check the 'Copyright Information' section for details of this license and what re-use is permitted. If your intended use exceeds what is permitted by the license or if you are unable to locate the licence and re-use information, please contact the Rights and Permissions team.
Uncontrolled Keywords : Budding yeast; Modeling; Origin activation; Replication profiles; Robustness
Depositing User : Clive Harris
Date Deposited : 16 Apr 2019 14:16
Last Modified : 16 Apr 2019 14:16

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