The eukaryotic bell-shaped temporal rate of DNA replication origin firing emanates from a balance between origin activation and passivation
- CNRS, Ecole Normale Supérieure de Lyon, France
- Ibitec-S, CEA, France
- Institut de Biologie de l'Ecole Normale Supérieure, France
- Laboratoire Ondes et Matière d'Aquitaine, France
Abstract
The time-dependent rate I(t) of origin firing per length of unreplicated DNA presents a universal bell shape in eukaryotes that has been interpreted as the result of a complex time-evolving interaction between origins and limiting firing factors. Here we show that a normal diffusion of replication fork components towards localized potential replication origins (p-oris) can more simply account for the I(t) universal bell shape, as a consequence of a competition between the origin firing time and the time needed to replicate DNA separating two neighboring p-oris. We predict the I(t) maximal value to be the product of the replication fork speed with the squared p-ori density. We show that this relation is robustly observed in simulations and in experimental data for several eukaryotes. Our work underlines that fork-component recycling and potential origins localization are sufficient spatial ingredients to explain the universality of DNA replication kinetics.
Data availability
All experimental data analyzed in this study are included in the manuscript. Source data files have been provided for Figure 2.
Article and author information
Author details
Funding
Institut National Du Cancer (PLBIO16-302)
- Olivier Hyrien
- Benjamin Audit
Fondation pour la Recherche Médicale (DEI20151234404)
- Arach Goldar
- Olivier Hyrien
- Benjamin Audit
Agence Nationale de la Recherche (ANR-15-CE12-0011-01)
- Olivier Hyrien
- Alain Arneodo
- Benjamin Audit
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Arbona et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,926
- views
-
- 300
- downloads
-
- 20
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
The eukaryotic bell-shaped temporal rate of DNA replication origin firing emanates from a balance between origin activation and passivation
eLife 7:e35192.
https://doi.org/10.7554/eLife.35192
