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

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.