Topoisomerase I prevents transcription-replication conflicts at transcription termination sites

Yaqun Liu; Yea-Lih Lin; Philippe Pasero; Chun-Long Chen

doi:10.1080/23723556.2020.1843951

Topoisomerase I prevents transcription-replication conflicts at transcription termination sites

Mol Cell Oncol. 2020 Dec 7;8(1):1843951. doi: 10.1080/23723556.2020.1843951.

Authors

Yaqun Liu¹, Yea-Lih Lin², Philippe Pasero², Chun-Long Chen¹

Affiliations

¹ Institut Curie, PSL Research University, CNRS, UMR3244, Sorbonne Université, Paris, France.
² Institut de Génétique Humaine, CNRS et Université de Montpellier, Montpellier, France.

Abstract

R-loops have both positive and negative impacts on chromosome functions. To identify toxic R-loops, we mapped RNA:DNA hybrids, markers of replication fork stalling and DNA double-strand breaks along the human genome. This analysis indicates that transient replication fork pausing occurs at the transcription termination sites of highly expressed genes enriched in R-loops and prevents head-on conflicts with transcription, in a topoisomerase I-dependent manner.

Keywords: R-loops; Transcription-replication conflict; chromosome breaks; topoisomerase I.

Grants and funding

Work of CC lab is supported by the YPI program of I. Curie, the IC3i grant of I. Curie, the ATIP-Avenir program from Centre national de la recherche scientifique (CNRS) and Plan Cancer, the Agence Nationale pour la Recherche (ANR) and Institut National du Cancer (INCa) [PLBIO19-076]. Work in the PP lab is supported by grants from the Agence Nationale pour la Recherche (ANR), Institut National du Cancer (INCa), the Ligue Nationale Contre le Cancer (équipe labellisée) and the Fondation MSDAvenir.