title: The DNA damage response in viral-induced cellular transformation.
abstract: The DNA damage response (DDR) has emerged as a critical tumour suppressor pathway responding to cellular DNA replicative stress downstream of aberrant oncogene over-expression. Recent studies have now implicated the DDR as a sensor of oncogenic virus infection. In this review, we discuss the mechanisms by which tumour viruses activate and also suppress the host DDR. The mechanism of tumour virus induction of the DDR is intrinsically linked to the need for these viruses to promote an S-phase environment to replicate their nucleic acid during infection. However, inappropriate expression of viral oncoproteins can also activate the DDR through various mechanisms including replicative stress, direct interaction with DDR components and induction of reactive oxygen species. Given the growth-suppressive consequences of activating the DDR, tumour viruses have also evolved mechanisms to attenuate these pathways. Aberrant expression of viral oncoproteins may therefore promote tumourigenesis through increased somatic mutation and aneuploidy due to DDR inactivation. This review will focus on the interplay between oncogenic viruses and the DDR with respect to cellular checkpoint control and transformation.
authors.affiliation: Department of Molecular Genetics and Microbiology, Center for Virology, Duke University Medical Center, 213 Research Dr., CARL 424, DUMC 3054, Durham, NC 27710, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Nikitin
authors.forename: M A
authors.initials: MA
authors.lastname: Luftig
mesh_terms: D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D004249:DNA Damage; D018816:Genes, cdc; D006801:Humans; D009858:Oncogenic Viruses / Q000502:physiology*; D014412:Tumor Virus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology*