Deciphering DNA Replication Dynamics in Eukaryotic Cell Populations in Relation with Their Averaged Chromatin Conformations

Overview

Journal Sci Rep

Specialty Science

Date 2016 Mar 4

PMID 26935043

Citations 5

Authors

A Goldar

A Arneodo

B Audit

F Argoul

A Rappailles

G Guilbaud

N Petryk

M Kahli

O Hyrien

Affiliations

Soon will be listed here.

Abstract

We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin's fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.

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The eukaryotic bell-shaped temporal rate of DNA replication origin firing emanates from a balance between origin activation and passivation.

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Phosphorylated SIRT1 associates with replication origins to prevent excess replication initiation and preserve genomic stability.

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