Mapping DNA double strand breaks in HeLa nuclei following etoposide and camptothecin treatment.

Using genome-wide DNA break mapping/sequencing techniques at single-nucleotide resolution, we found that DSBs are preferentially located around transcription start sites (TSSs) of highly transcribed and paused genes, and Pol II promoter-proximal pausing sites are enriched with DSBs. Inhibition of topoisomerase I and II by camptothecin and etoposide treatment, respectively, showed increasing DSBs at the pausing sites demonstrating the involvement of topoisomerases in the generation of DNA breaks at the pausing sites.