Transcription-dependent DNA double-strand breaks and human disease

Agnese Cristini; Natalia Gromak; Olivier Sordet

doi:10.1080/23723556.2019.1691905

Transcription-dependent DNA double-strand breaks and human disease

Mol Cell Oncol. 2020 Jan 10;7(2):1691905. doi: 10.1080/23723556.2019.1691905. eCollection 2020.

Authors

Agnese Cristini¹, Natalia Gromak¹, Olivier Sordet²

Affiliations

¹ Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
² Cancer Research Center of Toulouse, INSERM, Université de Toulouse, Université Toulouse III Paul Sabatier, CNRS, Toulouse, France.

Abstract

Accumulation of DNA damage in resting cells is an emerging cause of human disease. We identified a mechanism of DNA double-strand break (DSB) formation in non-replicating cells, which strictly depends on transcription. These transcriptional DSBs arise from the twinned processing of R-loops and topoisomerase I and may underlie neurological disorders and cancers.

Keywords: Cancer; DNA double-strand break; DNA repair; Neurodegenerative disease; R-loop; RNA/DNA hybrid; Senataxin; TDP1; Topoisomerase I; Transcription; XPF.

Abstract

Grants and funding