UPF1 promotes the formation of R loops to stimulate DNA double-strand break repair
| Autor: | Julia W. Grimstead, Duncan M. Baird, Greg H.P. Ngo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Genomic instability DNA Repair DNA repair Science General Physics and Astronomy DNA Single-Stranded Double-strand DNA breaks General Biochemistry Genetics and Molecular Biology Article Cell Line 03 medical and health sciences Nucleic acid thermodynamics chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Humans DNA Breaks Double-Stranded Cancer Multidisciplinary biology Base Sequence Chemistry RNA Helicase Nucleic Acid Hybridization General Chemistry DNA G2-M DNA damage checkpoint Telomere HCT116 Cells Double Strand Break Repair Cell biology 030104 developmental biology biology.protein Trans-Activators RNA Interference R-Loop Structures Homologous recombination 030217 neurology & neurosurgery RNA Helicases |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) |
| ISSN: | 2041-1723 |
| Popis: | 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. R loops are formed when single-stranded RNA anneals to one strand of DNA, forming three-stranded structures containing DNA-RNA hybrids and the displaced non-template single-stranded DNA. Here the authors reveal that the DNA:RNA helicase UPF1 plays a role in promoting R loops formation at telomeric double strand breaks to stimulate DNA resection and repair. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink