DNA replication timing reveals genome-wide features of transcription and fragility.

ABSTRACT: DNA replication in humans requires precise regulation to ensure accurate genome duplication and maintain genome integrity. A key indicator of this regulation is replication timing, which reflects the interplay between origin firing and fork dynamics. We present a high-resolution (1-kilobase) mathematical model that infers firing rate distributions from Repli-seq timing data across multiple cell lines, enabling a genome-wide comparison between predicted and observed replication. Notably, regions where the model and data diverge often overlap fragile sites and long genes, highlighting the influence of genomic architecture on replication dynamics. Conversely, regions of strong concordance are associated with open chromatin and active promoters, where elevated firing rates facilitate timely fo

SUBMITTER: Berkemeier F 

PROVIDER: S-EPMC12089344 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature