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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.

SUBMITTER: Hawkins M

PROVIDER: S-EPMC3898788 | biostudies-literature |

REPOSITORIES: biostudies-literature

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High-resolution genome replication profiles, modeling and single-cell imaging define the stochastic nature of replication initiation and termination

Project description:Eukaryotic genome replication is stochastic with each cell using a different cohort of replication origins. Interpreting high-resolution genome replication profiles with a mathematical model allowed us to quantify the stochastic nature of genome replication. This approach included estimation of the activity of every replication origin and the genome-wide location of replication termination events. Single-cell measurements verified the inferred values for stochastic origin replication time. Strains in which multiple origins had been inactivated, confirmed that the location 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. Measurement of genome replication time for two S. cerevisiae strains. For each strain six S phase samples werecompared with a non-replicating sample.

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