/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 DNA damage that is induced by bacterial infection, 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 of normal gastric epithelial cells significantly increases abasic sites (AP) that are repaired inefficiently or not at all 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. Our data suggest that /H. pylori/ induced BER intermediates are required to activate HDR pathways. Therefore, BER is one of the first lines of defense against /H. pylori/ induced DNA damage. This is followed by hand-off of the BER intermediates to HDR, in an attempt to maintain genomic integrity of gastric cells.