H. pylori-Induced DNA Strand Breaks Are Introduced by Nucleotide Excision Repair Endonucleases and Promote NF-κB Target Gene Expression.
Cell Rep
; 13(1): 70-79, 2015 Oct 06.
Article
em En
| MEDLINE
| ID: mdl-26411687
ABSTRACT
The human bacterial pathogen Helicobacter pylori exhibits genotoxic properties that promote gastric carcinogenesis. H. pylori introduces DNA double strand breaks (DSBs) in epithelial cells that trigger host cell DNA repair efforts. Here, we show that H. pylori-induced DSBs are repaired via error-prone, potentially mutagenic non-homologous end-joining. A genome-wide screen for factors contributing to DSB induction revealed a critical role for the H. pylori type IV secretion system (T4SS). Inhibition of transcription, as well as NF-κB/RelA-specific RNAi, abrogates DSB formation. DSB induction further requires ß1-integrin signaling. DSBs are introduced by the nucleotide excision repair endonucleases XPF and XPG, which, together with RelA, are recruited to chromatin in a highly coordinated, T4SS-dependent manner. Interestingly, XPF/XPG-mediated DNA DSBs promote NF-κB target gene transactivation and host cell survival. In summary, H. pylori induces XPF/XPG-mediated DNA damage through activation of the T4SS/ß1-integrin signaling axis, which promotes NF-κB target gene expression and host cell survival.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Proteínas Nucleares
/
Helicobacter pylori
/
Proteínas I-kappa B
/
Proteínas de Ligação a DNA
/
Endonucleases
/
Células Epiteliais
/
Quebras de DNA de Cadeia Dupla
/
Reparo do DNA por Junção de Extremidades
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article