Mechanism of DNA breaks by bacterial pathogen H. pylori

Mechanism of DNA breaks by bacterial pathogen H. pylori

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, scientists 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).

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/β1-integrin signaling axis, which promotes NF-κB target gene expression and host cell survival.

http://www.cell.com/cell-reports/abstract/S2211-1247(15)00987-0
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