Human Rad52 Promotes XPG-Mediated R-loop Processing to Initiate Transcription-Associated Homologous Recombination Repair.
Cell
; 175(2): 558-570.e11, 2018 10 04.
Article
em En
| MEDLINE
| ID: mdl-30245011
ABSTRACT
Given that genomic DNA exerts its function by being transcribed, it is critical for the maintenance of homeostasis that DNA damage, such as double-strand breaks (DSBs), within transcriptionally active regions undergoes accurate repair. However, it remains unclear how this is achieved. Here, we describe a mechanism for transcription-associated homologous recombination repair (TA-HRR) in human cells. The process is initiated by R-loops formed upon DSB induction. We identify Rad52, which is recruited to the DSB site in a DNA-RNA-hybrid-dependent manner, as playing pivotal roles in promoting XPG-mediated R-loop processing and initiating subsequent repair by HRR. Importantly, dysfunction of TA-HRR promotes DSB repair via non-homologous end joining, leading to a striking increase in genomic aberrations. Thus, our data suggest that the presence of R-loops around DSBs within transcriptionally active regions promotes accurate repair of DSBs via processing by Rad52 and XPG to protect genomic information in these critical regions from gene alterations.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Proteínas Nucleares
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Proteínas de Ligação a DNA
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Endonucleases
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Proteína Rad52 de Recombinação e Reparo de DNA
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Reparo de DNA por Recombinação
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article