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.
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All experimental data analyzed in this study are included in the manuscript. Source data files have been provided for Figure 2.
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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.
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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
