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Nat Commun ; 12(1): 5512, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535666

RESUMO

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.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA , DNA/metabolismo , Hibridização de Ácido Nucleico , Edição de RNA , RNA/metabolismo , Adenosina Desaminase/genética , Proteína BRCA1/metabolismo , Linhagem Celular Tumoral , DNA Helicases/metabolismo , Deleção de Genes , Genes Reporter , Instabilidade Genômica , Proteínas de Fluorescência Verde/metabolismo , Recombinação Homóloga/genética , Humanos , Enzimas Multifuncionais/metabolismo , Estabilidade Proteica , RNA Helicases/metabolismo , Proteínas de Ligação a RNA/genética , Proteína de Replicação A/metabolismo
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