1. Chromosomes and Gene Expression
  2. Computational and Systems Biology
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The eukaryotic bell-shaped temporal rate of DNA replication origin firing emanates from a balance between origin activation and passivation

  1. Jean-Michel Arbona
  2. Arach Goldar
  3. Olivier Hyrien
  4. Alain Arneodo
  5. Benjamin Audit  Is a corresponding author
  1. CNRS, Ecole Normale Supérieure de Lyon, France
  2. Ibitec-S, CEA, France
  3. Institut de Biologie de l'Ecole Normale Supérieure, France
  4. Laboratoire Ondes et Matière d'Aquitaine, France
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Cite this article as: eLife 2018;7:e35192 doi: 10.7554/eLife.35192

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.

Article and author information

Author details

  1. Jean-Michel Arbona

    Laboratoire de Physique, ENS de Lyon, CNRS, Ecole Normale Supérieure de Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Arach Goldar

    Ibitec-S, CEA, Gif-sur-Yvette, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Olivier Hyrien

    Institut de Biologie de l'Ecole Normale Supérieure, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8879-675X
  4. Alain Arneodo

    Université de Bordeaux - CNRS UMR5798, Laboratoire Ondes et Matière d'Aquitaine, Talence, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Benjamin Audit

    Laboratoire de Physique, ENS de Lyon, CNRS, Ecole Normale Supérieure de Lyon, Lyon, France
    For correspondence
    benjamin.audit@ens-lyon.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2683-9990

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.

Reviewing Editor

  1. Bruce Stillman, Cold Spring Harbor Laboratory, United States

Publication history

  1. Received: January 18, 2018
  2. Accepted: May 31, 2018
  3. Accepted Manuscript published: June 1, 2018 (version 1)
  4. Version of Record published: July 5, 2018 (version 2)

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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