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

Jean-Michel Arbona (1) , Arach Goldar (2, 3) , Olivier Hyrien (4) , Alain Arneodo (5, 1) , Benjamin Audit (1)

1 Phys-ENS - Laboratoire de Physique de l'ENS Lyon
2 GTR - Régulation transcriptionnelle des génomes
3 LBI - Laboratoire de Biologie Intégrative
4 IBENS - Institut de biologie de l'ENS Paris
5 LOMA - Laboratoire Ondes et Matière d'Aquitaine

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.

Domaines: Matière Molle [cond-mat.soft]; Biophysique [physics.bio-ph]; Biophysique; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Jean-Michel Arbona, Arach Goldar, Olivier Hyrien, Alain Arneodo, Benjamin Audit. The eukaryotic bell-shaped temporal rate of DNA replication origin firing emanates from a balance between origin activation and passivation. eLife, 2018, 7, pp.e35192. ⟨10.7554/eLife.35192⟩. ⟨hal-01837938⟩