title: Helicobacter pylori Infection Causes Characteristic DNA Damage Patterns in Human Cells.
abstract: Infection with the human pathogen Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer. Since the bacterium exerts multiple genotoxic effects, we examined the circumstances of DNA damage accumulation and identified regions within the host genome with high susceptibility to H. pylori-induced damage. Infection impaired several DNA repair factors, the extent of which depends on a functional cagPAI. This leads to accumulation of a unique DNA damage pattern, preferentially in transcribed regions and proximal to telomeres, in both gastric cell lines and primary gastric epithelial cells. The observed pattern correlates with focal amplifications in adenocarcinomas of the stomach and partly overlaps with known cancer genes. We thus demonstrate an impact of a bacterial infection directed toward specific host genomic regions and describe underlying characteristics that make such regions more likely to acquire heritable changes during infection, which could contribute to cellular transformation.
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Koeppel
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Fernando
authors.initials: F
authors.lastname: Garcia-Alcalde
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Frithjof
authors.initials: F
authors.lastname: Glowinski
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schlaermann
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: meyer@mpiib-berlin.mpg.de.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Meyer
mesh_terms: D004249:DNA Damage; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology; D005784:Gene Amplification; D015894:Genome, Human; D016481:Helicobacter Infections / Q000235:genetics* / Q000473:pathology; D006801:Humans; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics
chemical_list: D020794:Receptor Protein-Tyrosine Kinases