Abstract
The time-dependent rate [Formula: see text] 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 [Formula: see text] 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 [Formula: see text] 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.
Highlights
Eukaryotic DNA replication is a stochastic process (Hyrien et al, 2013; Hawkins et al, 2013; Hyrien, 2016)
The time-dependent rate of origin firing per length of unreplicated DNA, I(t), is a fundamental parameter of DNA replication kinetics
As previously simulated in human (Löb et al, 2016), we model the entry in S-phase using an exponentially relaxed loading of the firing factors with a time scale shorter than the S-phase duration Tphase (3 mins for Xenopus embryo, where Tphase ∼ 30 mins, and 10 mins for S. cerevisiae, where Tphase ∼ 60 mins)
Summary
Eukaryotic DNA replication is a stochastic process (Hyrien et al, 2013; Hawkins et al, 2013; Hyrien, 2016). When the rate of fork mergers increases due to the fact that there are as many active forks but a smaller length of unreplicated DNA, the number of free firing factors increases up to NDT at the end of S-phase.
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