TY - JOUR T1 - ADAR2-mediated RNA editing of DNA:RNA hybrids is required for DNA double strand break repair JF - bioRxiv DO - 10.1101/2021.03.24.436729 SP - 2021.03.24.436729 AU - Sonia Jimeno AU - Rosario Prados-Carvajal AU - María Jesús Fernández-Ávila AU - Sonia Silva AU - Domenico Alessandro Silvestris AU - Martín Endara-Coll AU - Judit Domingo-Prim AU - Fernando Mejías-Navarro AU - Guillermo Rodríguez-Real AU - Amador Romero-Franco AU - Silvia Jimeno-González AU - Sonia Barroso AU - Valeriana Cesarini AU - Andrés Aguilera AU - Angela Gallo AU - Neus Visa AU - Pablo Huertas Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/03/24/2021.03.24.436729.abstract N2 - 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 RNA Editing DAmage Response (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.One sentence summary: DNA recombination requires RNA editing of DNA:RNA hybrids to ease their melting and facilitate DNA end resectionCompeting Interest StatementThe authors have declared no competing interest. ER -