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High-resolution replication profiles define the stochastic nature of genome replication initiation and termination

Hawkins, Michelle; Retkute, Renata; Müller, Carolin A.; Saner, Nazan; Tanaka, Tomoyuki U.; de Moura, Alessandro P.S.; Nieduszynski, Conrad A.

Authors

Michelle Hawkins

Renata Retkute

Carolin A. Müller

Nazan Saner

Tomoyuki U. Tanaka

Alessandro P.S. de Moura

Conrad A. Nieduszynski

Abstract

Eukaryotic genome replication is stochastic, and each cell uses a different cohort of replication origins. We demonstrate that interpreting high-resolution Saccharomyces cerevisiae genome replication data with a mathematical model allows quantification of the stochastic nature of genome replication, including the efficiency of each origin and the distribution of termination events. Single-cell measurements support the inferred values for stochastic origin activation time. A strain, in which three origins were inactivated, confirmed that the distribution of termination events is primarily dictated by the stochastic activation time of origins. Cell-to-cell variability in origin activity ensures that termination events are widely distributed across virtually the whole genome. We propose that the heterogeneity in origin usage contributes to genome stability by limiting potentially deleterious events from accumulating at particular loci.

Journal Article Type Article
Publication Date Nov 7, 2013
Journal Cell Reports
Print ISSN 2211-1247
Electronic ISSN 2211-1247
Publisher Elsevier (Cell Press)
Peer Reviewed Peer Reviewed
Volume 5
Issue 4
Institution Citation Hawkins, M., Retkute, R., Müller, C. A., Saner, N., Tanaka, T. U., de Moura, A. P., & Nieduszynski, C. A. (2013). High-resolution replication profiles define the stochastic nature of genome replication initiation and termination. Cell Reports, 5(4), doi:10.1016/j.celrep.2013.10.014
DOI https://doi.org/10.1016/j.celrep.2013.10.014
Publisher URL http://www.sciencedirect.com/science/article/pii/S2211124713005834
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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