Chromatin context shapes DNA damage formation and nucleotide excision repair dynamics in Caenorhabditis elegans

Official URL: https://dx.doi.org/10.1093/nar/gkaf1080

DNA damage formation and repair are influenced by the genomic landscape, yet how chromatin and transcriptional activity shape these processes at a whole-organism scale remains incompletely understood. Using Caenorhabditis elegans, a widely used model organism to study DNA repair and related processes, we present comprehensive, time-course maps of ultraviolet-induced DNA damage and excision repair, revealing how chromatin context and transcription dictate the spatiotemporal patterns of damage and repair. Of the two repair pathways—global repair and transcription-coupled repair—global repair predominates, removing the majority of the lesions; and notably, (6–4) photoproducts are removed by transcription-coupled repair at an extent comparable to cyclobutane pyrimidine dimers, a feature not previously observed in animals. Integration of damage and repair profiles with chromatin features reveals that, despite non-uniform damage formation, repair efficiency is the primary determinant of residual damage. Finally, repair around accessible regions exhibit nucleosome-size periodicity, reflecting underlying nucleosome architecture. Together, these findings establish C. elegans as a valuable model organism for interrogating damage formation and repair within a chromatin context and reveal species-specific features that broaden our understanding of DNA repair mechanisms across metazoans.