title: Human T-lymphotropic type 1 virus p30 inhibits homologous recombination and favors unfaithful DNA repair.
abstract: Whereas oncogenic retroviruses are common in animals, human T-lymphotropic virus 1 (HTLV-1) is the only transmissible retrovirus associated with cancer in humans and is etiologically linked to adult T-cell leukemia. The leukemogenesis process is still largely unknown, but relies on extended survival and clonal expansion of infected cells, which in turn accumulate genetic defects. A common feature of human tumor viruses is their ability to stimulate proliferation and survival of infected pretumoral cells and then hide by establishing latency in cells that have acquired a transformed phenotype. Whereas disruption of the DNA repair is one of the major processes responsible for the accumulation of genomic abnormalities and carcinogenesis, the absence of DNA repair also poses the threat of cell-cycle arrest or apoptosis of virus-infected cells. This study describes how the HTLV-1 p30 viral protein inhibits conservative homologous recombination (HR) DNA repair by targeting the MRE11/RAD50/NBS1 complex and favors the error-prone nonhomologous-end-joining (NHEJ) DNA-repair pathway instead. As a result, HTLV-1 p30 may facilitate the accumulation of mutations in the host genome and the cumulative risk of transformation. Our results provide new insights into how human tumor viruses may manipulate cellular DNA-damage responses to promote cancer.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
authors.forename: Hicham H
authors.initials: HH
authors.lastname: Baydoun
authors.forename: Joanna
authors.initials: J
authors.lastname: Pancewicz
authors.forename: Christophe
authors.initials: C
authors.lastname: Nicot
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle; D002467:Cell Nucleus; D002478:Cells, Cultured; D003593:Cytoplasm; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D015368:Human T-lymphotropic virus 1; D006801:Humans; D047468:Immunoprecipitation; D021381:Protein Transport; D011995:Recombination, Genetic / Q000235:genetics*; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D012191:Retroviridae Proteins; C072814:tof protein, Human T-lymphotropic virus 1