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. and Nieduszynski, Conrad A. ORCID: https://orcid.org/0000-0003-2001-076X (2013) High-resolution replication profiles define the stochastic nature of genome replication initiation and termination. Cell Reports, 5 (4). pp. 1132-1141. ISSN 2211-1247

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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 quantificationof 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

Item Type: Article
Additional Information: Funding Information: This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC; BB/E023754/1, BB/ G001596/1, BB/F00513X/1, and BB/K007211/1) and the Wellcome Trust (080737, 081918, 083524, and 096535). C.A.N. is a BBSRC David Phillips Fellow. T.U.T. is a Wellcome Trust Principal Research Fellow.
Uncontrolled Keywords: biochemistry, genetics and molecular biology(all) ,/dk/atira/pure/subjectarea/asjc/1300
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 07 Sep 2022 15:30
Last Modified: 21 Oct 2022 01:37
URI: https://ueaeprints.uea.ac.uk/id/eprint/87868
DOI: 10.1016/j.celrep.2013.10.014

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