title: What's the damage? The impact of pathogens on pathways that maintain host genome integrity.
abstract: Maintaining genome integrity and transmission of intact genomes is critical for cellular, organismal, and species survival. Cells can detect damaged DNA, activate checkpoints, and either enable DNA repair or trigger apoptosis to eliminate the damaged cell. Aberrations in these mechanisms lead to somatic mutations and genetic instability, which are hallmarks of cancer. Considering the long history of host-microbe coevolution, an impact of microbial infection on host genome integrity is not unexpected, and emerging links between microbial infections and oncogenesis further reinforce this idea. In this review, we compare strategies employed by viruses, bacteria, and parasites to alter, subvert, or otherwise manipulate host DNA damage and repair pathways. We highlight how microbes contribute to tumorigenesis by directly inducing DNA damage, inactivating checkpoint controls, or manipulating repair processes. We also discuss indirect effects resulting from inflammatory responses, changes in cellular metabolism, nuclear architecture, and epigenome integrity, and the associated evolutionary tradeoffs.
authors.affiliation: Division of Cancer Pathobiology, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address: weitzmanm@email.chop.edu.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Weitzman
authors.affiliation: University Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate, UMR 7216 CNRS, 75013 Paris, France. Electronic address: jonathan.weitzman@univ-paris-diderot.fr.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Weitzman
mesh_terms: D017209:Apoptosis; D001424:Bacterial Infections / Q000150:complications / Q000473:pathology; D004249:DNA Damage; D004260:DNA Repair; D042822:Genomic Instability; D054884:Host-Pathogen Interactions; D009154:Mutation; D009369:Neoplasms / Q000473:pathology; D010272:Parasitic Diseases / Q000150:complications / Q000473:pathology; D014777:Virus Diseases / Q000150:complications / Q000473:pathology