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UPF1 promotes the formation of R loops to stimulate DNA double-strand break repair

Ngo, Greg H. P., Grimstead, Julia W. and Baird, Duncan M. 2021. UPF1 promotes the formation of R loops to stimulate DNA double-strand break repair. Nature Communications 12 , 3849. 10.1038/s41467-021-24201-w

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Abstract

DNA-RNA hybrid structures have been detected at the vicinity of DNA double-strand breaks (DSBs) occurring within transcriptional active regions of the genome. The induction of DNA-RNA hybrids strongly affects the repair of these DSBs, but the nature of these structures and how they are formed remain poorly understood. Here we provide evidence that R loops, three-stranded structures containing DNA-RNA hybrids and the displaced single-stranded DNA (ssDNA) can form at sub-telomeric DSBs. These R loops are generated independently of DNA resection but are induced alongside two-stranded DNA-RNA hybrids that form on ssDNA generated by DNA resection. We further identified UPF1, an RNA/DNA helicase, as a crucial factor that drives the formation of these R loops and DNA-RNA hybrids to stimulate DNA resection, homologous recombination, microhomology-mediated end joining and DNA damage checkpoint activation. Our data show that R loops and DNA-RNA hybrids are actively generated at DSBs to facilitate DNA repair.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Nature Research
ISSN: 2041-1723
Funders: Cancer Research UK
Date of First Compliant Deposit: 8 June 2021
Date of Acceptance: 7 June 2021
Last Modified: 27 Feb 2022 12:08
URI: https://orca.cardiff.ac.uk/id/eprint/141789

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