New preprint: how origin firing constrains DNA replication completion

I am pleased to share our new preprint, “Completion of DNA replication is constrained by the spatiotemporal organisation of origin firing”, with Ahmad Alkhaled, Michael A. Boemo, and Katerina Nik.

DNA replication must duplicate the entire genome before a cell divides, yet the activation of replication origins is inherently stochastic. This creates the classical random completion problem: how can many probabilistic, local initiation events reliably ensure that no region of the genome is left unfinished?

In this work, we introduce a population-level kinetic framework that extends nucleation-and-growth models by tracking unreplicated regions across their size, genomic position, and time. The model lets us quantify how both the density and spatial organisation of origin firing constrain the final stages of replication.

Alongside establishing the mathematical well-posedness of the system, we derive computable bounds on the fraction of cells that remain unreplicated at the most vulnerable genomic loci and on the time required for loci to approach complete replication. These results provide a rigorous route from local initiation patterns to genome-wide completion, with potential applications to understanding replication stress and genome instability.

This project has been a rewarding collaboration at the interface of applied mathematics and DNA replication biology, bringing together partial differential equations, stochastic replication dynamics, and questions of genome maintenance.

Read the work: arXiv:2609.07924