Abstract LB-150: Carcinogenic Helicobacter pylori infection induces base excision repair intermediates to trigger homologous-dependent repair in human gastric epithelial cells.

Abstract

Abstract Helicobacter pylori infection of the human stomach is associated with disease-causing inflammation that elicits DNA damage in both bacterial and host cells. To investigate base excision repair (BER) as the first line of defense against bacterial infection to maintain host cell genomic stability, we examined H. pylori induced BER intermediates that could be responsible for double strand break (DSB) and homologous dependent repair (HDR). Here, we show that H. pylori infection significantly increases abasic sites (AP) that are not repaired by BER. As a result, unrepaired BER intermediates lead to slow replication fork speed and replication fork collapse that eventually is converted to double strand breaks. To determine if H. pylori infection enhances recombinational repair to process DSBs, we have analyzed the cells for homologous directed repair pathways. Direct measurement of HDR using a GFP-based assay demonstrates significantly increased HDR in cells infected with H. pylori. Our data suggest that H. pylori induced BER intermediates are required to activate homologous directed repair pathways. Therefore, our finding suggests that BER is the first line of defense against H. pylori induced DNA damage followed by HDR, to maintain genomic integrity of gastric cells. Citation Format: Dawit Kidane, Drew L Murphy, Joann.B Sweasy. Carcinogenic Helicobacter pylori infection induces base excision repair intermediates to trigger homologous-dependent repair in human gastric epithelial cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-150. doi:10.1158/1538-7445.AM2013-LB-150