Helicobacter pylori (H.pylori) infection is a significant risk factor for gastric cancer (GC) development. Growing body of evidence outlines a causal link between infection with H.pylori and increased DNA breakage in host cell. While several mechanisms have been proposed for this damage, their relative impact on the overall bacterial genotoxicity is unknown. Moreover, the link between the formation of DNA damage upon infection and the emergence of cancerous structural variants (SV) in the genome of infected cells remained unexplored.

In this project we aim to characterize the mechanisms that drive H.pylori genotoxicity and their relation to the development of gastric cancer.

High-resolution map of genomic H.pylori-induced recurrent break sites, revealed distinct pattern of H.pylori-mediated breaks across the genome. These breaks were found to be replication-coupled, and dependent of depletion of dNTPs by the bacteria.

Furthermore, the sites of these breaks are reflected in structural variants from intestinal-type GC patients.