Genome-wide integration of chromatin accessibility and endogenous DNA break signals across cancer cell lines

Abstract Endogenous DNA breaks arise during normal cellular processes and can compromise genome stability if not properly repaired. Chromatin accessibility may influence both DNA break formation and repair, yet its relationship with endogenous DNA break landscapes in cancer cells remains unclear. Here, we integrated ATAC-seq with mDEtail-seq across 20 samples from 10 human cancer cell lines to examine this relationship. DNA break signals showed a positive association with chromatin accessibility, with the highest signal levels observed in the most accessible regions. Similarly, accessible chromatin regions near transcription start sites exhibited higher DNA break signals than corresponding inaccessible regions, whereas gene expression levels showed no detectable association with DNA break signals across five cell lines. In addition, accessible chromatin regions contained a greater fraction of DNA break signals than expected from their genomic coverage. These results suggest that endogenous DNA breaks are preferentially associated with accessible chromatin rather than gene expression, providing a genome-wide view of DNA break distribution in cancer cells.