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

TL;DR

This study explores how chromatin and transcription influence DNA damage and repair in C. elegans, revealing new insights into repair mechanisms.

Contribution

The study reveals species-specific DNA repair dynamics and the role of chromatin in shaping repair efficiency in C. elegans.

Findings

Global repair predominates in removing UV-induced DNA lesions in C. elegans.

(6–4) photoproducts are efficiently removed by transcription-coupled repair, a novel finding in animals.

Repair efficiency, not damage formation, determines residual DNA damage in chromatin contexts.

Abstract

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.

Graphical Abstract

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