Artículo
ADAR-mediated RNA editing of DNA:RNA hybrids is required for DNA double strand break repair
Autor/es | Jimeno González, Sonia
Prados Carvajal, Rosario Fernández Ávila, María Jesús Pinela Da Silva, Sonia Cristina Silvestris, Domenico Alessandro Endara Coll, Martin Rodríguez Real, Guillermo Domingo Prim, Judit Mejías Navarro, Fernando Romero Franco, Amador Jimeno González, Silvia Barroso, Sonia Cesarini, Valeriana Aguilera López, Andrés Gallo, Angela Visa, Neus Huertas Sánchez, Pablo |
Departamento | Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2021 |
Fecha de depósito | 2021-09-21 |
Publicado en |
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Resumen | 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 ... 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. |
Agencias financiadoras | Agencia Estatal de Investigación. España PID2019-104195GB-I00, AEI/10.13039/501100011033 |
Identificador del proyecto | PID2019-104195GB-I00
AEI/10.13039/501100011033 SAF2016-74855-P BFU2016-75058-P ERC2014 AdG669898 AIRC IG 22080 2015-04553 CAN 2016/460 |
Cita | Jimeno González, S., Prados Carvajal, R., Fernández Ávila, M.J., Pinela Da Silva, S.C., Silvestris, D.A., Endara Coll, M.,...,Huertas Sánchez, P. (2021). ADAR-mediated RNA editing of DNA:RNA hybrids is required for DNA double strand break repair. Nature Communications, 12 (1), 5512. |
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ADAR-mediated RNA.pdf | 1.787Mb | [PDF] | Ver/ | |