Work

Dynamic genome-wide mapping reveals how chromatin context shapes OGG1-mediated repair and related mutagenesis in human cells

Year: 2025

Type: article

Abstract: Potassium bromate-induced DNA damage, including 8-oxo-7,8-dihydroguanine (OG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG), are common oxidatively generated DNA lesions with mutagenic potential if not efficiently repaired. While sequencing-based studies have shown that damage formation is influenced by DNA sequence context, secondary structures, and chromatin features, how OGG1-mediated repair is regulated within chromatin remains unclear. Here, we apply CLAPS-seq to generate genome-wide, single-nucleotide resolution maps of OGG1-mediated repair over time in human cells, and systematically analyze how chromatin context affects repair efficiency across hierarchical scales. We find that chromatin accessibility governs rapid initial repair, whereas higher-order chromatin structures increasingly influence later-phase repair. In addition, nucleosome occupancy and transcription factor binding, exemplified by CCCTC-binding factor (CTCF), modulate OGG1-mediated repair at both local and base scales. Overall, mutational outcomes correlate more strongly with repair dynamics than with damage levels. Together, these findings establish a comprehensive framework linking chromatin organization, DNA repair kinetics, and oxidatively induced mutagenesis, and offer new insights into the origins of mutation patterns in cancer and diseases associated with oxidative stress.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkaf1330