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

Greg H. P. Ngo, Julia W. Grimstead and Duncan M. Baird ()
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Greg H. P. Ngo: Cardiff University
Julia W. Grimstead: Cardiff University
Duncan M. Baird: Cardiff University

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24201-w

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