title: High-resolution replication profiles define the stochastic nature of genome replication initiation and termination.
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.
authors.affiliation: Centre for Genetics and Genomics, School of Life Sciences, Queen's Medical Centre, The University of Nottingham, Nottingham NG7 2UH, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Hawkins
authors.forename: Renata
authors.initials: R
authors.lastname: Retkute
authors.forename: Carolin A
authors.initials: CA
authors.lastname: Müller
authors.forename: Nazan
authors.initials: N
authors.lastname: Saner
authors.forename: Tomoyuki U
authors.initials: TU
authors.lastname: Tanaka
authors.forename: Alessandro P S
authors.initials: AP
authors.lastname: de Moura
authors.forename: Conrad A
authors.initials: CA
authors.lastname: Nieduszynski
mesh_terms: D001483:Base Sequence; D004261:DNA Replication / Q000235:genetics*; D016681:Genome, Fungal / Q000235:genetics; D042822:Genomic Instability; D008962:Models, Theoretical; D018741:Replication Origin / Q000235:genetics*; D016196:S Phase / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D017422:Sequence Analysis, DNA