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

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

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Authors

Michelle Hawkins

Renata Retkute

Carolin A. M�ller

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.

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), https://doi.org/10.1016/j.celrep.2013.10.014

Journal Article Type Article
Publication Date Nov 7, 2013
Deposit Date Apr 15, 2014
Publicly Available Date Apr 15, 2014
Journal Cell Reports
Print ISSN 2211-1247
Electronic ISSN 2211-1247
Publisher Cell Press
Peer Reviewed Peer Reviewed
Volume 5
Issue 4
DOI https://doi.org/10.1016/j.celrep.2013.10.014
Public URL https://nottingham-repository.worktribe.com/output/719632
Publisher URL http://www.sciencedirect.com/science/article/pii/S2211124713005834

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