The human HELQ helicase and XRN2 exoribonuclease cooperate in R-loop resolution

Pan, J. M.; Betts, H.; Cubbon, A.; Bolt, E. L.; Soultanas, P.; He, L.

Abstract

The human HELQ helicase is a superfamily 2, 3’-5’ helicase homologous to POLQ and RNA helicases of the Ski2-like subfamily. It is involved in diverse aspects of DNA repair and is an emerging prognosis biomarker and novel drug-target for cancer therapy. HELQ interacts with RPA via its inherently disordered N-HELQ domain and hence recruited to RPA-bound DNA substrates. Our study reveals a novel role for HELQ in R-loop resolution. We show in cells and in vitro that HELQ is recruited by RPA at R-loops, which are then resolved if HELQ is catalytically active as an ATPase/helicase. Furthermore, we identify a functional interaction of HELQ with XRN2, a nuclear 5’ to 3’ exoribonuclease, which we suggest coordinates R-loop unwinding by HELQ with RNA digestion by XRN2. Collectively, we assign a new biological function for HELQ in genome stability in metazoans through its involvement with XRN2 in R-loop metabolism.

Citation

Pan, J. M., Betts, H., Cubbon, A., Bolt, E. L., Soultanas, P., & He, L. (2025). The human HELQ helicase and XRN2 exoribonuclease cooperate in R-loop resolution. Open Biology, 15(2), https://doi.org/10.1098/rsob.240112

• Journal Article Type: Article
• Acceptance Date: Sep 2, 2024
• Online Publication Date: Feb 19, 2025
• Publication Date: 2025-02
• Deposit Date: Sep 7, 2024
• Publicly Available Date: Sep 24, 2024
• Journal: Open Biology
• Electronic ISSN: 2046-2441
• Publisher: The Royal Society
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 2
• DOI: https://doi.org/10.1098/rsob.240112
• Keywords: HELQ helicase; XRN2 exoribonuclease; R-loops; RPA; DNA repair
• Public URL: https://nottingham-repository.worktribe.com/output/39251980
• Publisher URL: https://royalsocietypublishing.org/doi/10.1098/rsob.240112
• Additional Information: Received: 2024-05-01; Revised: 2025-01-14; Accepted: 2025-01-14; Published: 2025-02-19