DNA breaks at RNA Pol II pausing sites

DNA double-stranded breaks (DSBs) are strongly associated with active transcription. Using genome-wide DNA break mapping techniques at single-nucleotide resolution, we investigated the DNA DSB distribution around transcription start sites (TSSs). We found that DSBs are enriched at the TSSs of highly transcribed and paused genes, and RNA polymerase II promoter-proximal pausing sites are decorated with DNA DSBs. DSB intensity at pausing sites increases as the strength of pausing increases, regardless of whether the pausing sites are near or far from annotated TSSs. Inhibition of topoisomerase II by etoposide treatment demonstrated the involvement of topoisomerase in the generation of DNA breaks at the pausing sites.