ADAR-mediated RNA editing of DNA:RNA hybrids is required for DNA double strand break repair

• Published in: Nature communications Vol. 12; no. 1; pp. 5512 - 15
• Main Authors: Jimeno, Sonia, Prados-Carvajal, Rosario, Fernández-Ávila, María Jesús, Silva, Sonia, Silvestris, Domenico Alessandro, Endara-Coll, Martín, Rodríguez-Real, Guillermo, Domingo-Prim, Judit, Mejías-Navarro, Fernando, Romero-Franco, Amador, Jimeno-González, Silvia, Barroso, Sonia, Cesarini, Valeriana, Aguilera, Andrés, Gallo, Angela, Visa, Neus, Huertas, Pablo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.09.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/109; 14; 14/63; 38/23; 38/89; 38/91; 631/337/1427/2190; 631/337/1645/1944; 82/29; Adenosine; Adenosine Deaminase - genetics; BRCA1 Protein - metabolism; Cell Line, Tumor; Damage; Deoxyribonucleic acid; Depletion; DNA; DNA - metabolism; DNA Breaks, Double-Stranded; DNA damage; DNA Helicases - metabolism; DNA Repair; Editing; Gene Deletion; Genes, Reporter; Genomic Instability; Genotoxic chemicals; Genotoxicity; Green Fluorescent Proteins - metabolism; Homeostasis; Homologous recombination; Homologous Recombination - genetics; Homology; Humanities and Social Sciences; Humans; Hybrids; Kinases; multidisciplinary; Multifunctional Enzymes - metabolism; Nucleic Acid Hybridization; Nucleotide sequence; Post-transcription; Protein Stability; Repair; Replication Protein A - metabolism; Ribonucleic acid; RNA; RNA - metabolism; RNA Editing; RNA Helicases - metabolism; RNA-Binding Proteins - genetics; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-25790-2

The maintenance of genomic stability requires the coordination of multiple cellular tasks upon the appearance of DNA lesions. RNA editing, the post-transcriptional sequence alteration of RNA, has a profound effect on cell homeostasis, but its implication in the response to DNA damage was not previously explored. Here we show that, in response to DNA breaks, an overall change of the Adenosine-to-Inosine RNA editing is observed, a phenomenon we call the R NA E diting DA mage R esponse (REDAR). REDAR relies on the checkpoint kinase ATR and the recombination factor CtIP. Moreover, depletion of the RNA editing enzyme ADAR2 renders cells hypersensitive to genotoxic agents, increases genomic instability and hampers homologous recombination by impairing DNA resection. Such a role of ADAR2 in DNA repair goes beyond the recoding of specific transcripts, but depends on ADAR2 editing DNA:RNA hybrids to ease their dissolution. Different roles of specific RNA-related factors in DNA repair have now been reported. Here the authors reveal a role for RNA-editing by ADAR in DNA end resection following double strand break formation and a change in pattern of ADAR2-mediated A-to-I editing.