High-Resolution Replication Profiles Define the Stochastic Nature of Genome Replication Initiation and Termination

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

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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.
Original languageEnglish
Pages (from-to)1132-1141
Number of pages10
JournalCell Reports
Volume5
Issue number4
DOIs
Publication statusPublished - Nov 2013

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Genes
Genome
Replication Origin
Chemical activation
Genomic Instability
Saccharomyces cerevisiae
Theoretical Models
Yeast
Mathematical models

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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.

In: Cell Reports, Vol. 5, No. 4, 11.2013, p. 1132-1141.

Research output: Contribution to journalArticle

Hawkins, Michelle ; Retkute, Renata ; Müller, Carolin A ; Saner, Nazan ; Tanaka, Tomoyuki U ; de Moura, Alessandro P S ; Nieduszynski, Conrad A. / High-Resolution Replication Profiles Define the Stochastic Nature of Genome Replication Initiation and Termination. In: Cell Reports. 2013 ; Vol. 5, No. 4. pp. 1132-1141.
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AU - de Moura, Alessandro P S

AU - Nieduszynski, Conrad A

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