Completion of DNA replication is constrained by the spatiotemporal organisation of origin firing
Abstract
DNA replication requires the coordination of origin firing and fork progression to ensure the entire genome is timely duplicated before cell division. Yet origin firing is stochastic, giving rise to the classical random completion problem of how probabilistic local events can nevertheless ensure reliable genome duplication. Although several biological mechanisms have been proposed to resolve this problem, a quantitative account of how heterogeneous initiation and fork speed govern the persistence of the final unreplicated regions is still lacking. To address this gap, we introduce a population-level kinetic framework that extends KJMA nucleation-and-growth models by tracking unreplicated intervals over size, genomic position and time. We establish well-posedness of the resulting mean-field system and global existence for compatible data. Notably, by introducing a local initiation mass function, we quantify how the density and spatial organisation of origin firing constrain replication completion, yielding novel and sharp upper bounds on both the worst-locus unreplicated fraction and locuswise near-completion time. These results provide a rigorous and computable foundation for mapping vulnerabilities in replication completion and relating persistent unreplicated regions to replication stress and genome instability.
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BibTeX
@misc{alkhaled2026completion,
title = {{Completion of DNA replication is constrained by the spatiotemporal organisation of origin firing}},
author = {Ahmad Alkhaled and Francisco Berkemeier and Michael A. Boemo and Katerina Nik},
howpublished = {arXiv},
year = {2026},
month = sep,
doi = {10.48550/arxiv.2609.07924},
eprint = {2609.07924},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2609.07924},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Completion of DNA replication is constrained by the spatiotemporal organisation of origin firing
AU - Ahmad Alkhaled
AU - Francisco Berkemeier
AU - Michael A. Boemo
AU - Katerina Nik
PY - 2026
DA - 2026/09/07
PB - arXiv
DO - 10.48550/arxiv.2609.07924
UR - https://arxiv.org/abs/2609.07924
AB - DNA replication requires the coordination of origin firing and fork progression to ensure the entire genome is timely duplicated before cell division. Yet origin firing is stochastic, giving rise to the classical random completion problem of how probabilistic local events can nevertheless ensure reliable genome duplication. Although several biological mechanisms have been proposed to resolve this problem, a quantitative account of how heterogeneous initiation and fork speed govern the persistence of the final unreplicated regions is still lacking. To address this gap, we introduce a population-level kinetic framework that extends KJMA nucleation-and-growth models by tracking unreplicated intervals over size, genomic position and time. We establish well-posedness of the resulting mean-field system and global existence for compatible data. Notably, by introducing a local initiation mass function, we quantify how the density and spatial organisation of origin firing constrain replication completion, yielding novel and sharp upper bounds on both the worst-locus unreplicated fraction and locuswise near-completion time. These results provide a rigorous and computable foundation for mapping vulnerabilities in replication completion and relating persistent unreplicated regions to replication stress and genome instability.
ER -