title: Up-regulation of the error-prone DNA polymerase {kappa} promotes pleiotropic genetic alterations and tumorigenesis.
abstract: It is currently widely accepted that genetic instability is key to cancer development. Many types of cancers arise as a consequence of a gradual accumulation of nucleotide aberrations, each mutation conferring growth and/or survival advantage. Genetic instability could also proceed in sudden bursts leading to a more drastic upheaval of structure and organization of the genome. Genetic instability, as an operative force, will produce genetic variants and the greater the instability, the larger the number of variants. We report here that the overexpression of human DNA polymerase kappa, an error-prone enzyme that is up-regulated in lung cancers, induces DNA breaks and stimulates DNA exchanges as well as aneuploidy. Probably as the result of so many perturbations, excess polymerase kappa favors the proliferation of competent tumor cells as observed in immunodeficient mice. These data suggest that altered regulation of DNA metabolism might be related to cancer-associated genetic changes and phenotype.
authors.affiliation: Institute of Pharmacology and Structural Biology, Centre National de la Recherche Scientifique, Toulouse, France.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Bavoux
authors.forename: Andréia Machado
authors.initials: AM
authors.lastname: Leopoldino
authors.forename: Valérie
authors.initials: V
authors.lastname: Bergoglio
authors.forename: Jiyang
authors.initials: J
authors.lastname: O-Wang
authors.forename: Tomoo
authors.initials: T
authors.lastname: Ogi
authors.forename: Anne
authors.initials: A
authors.lastname: Bieth
authors.forename: Jean-Gabriel
authors.initials: JG
authors.lastname: Judde
authors.forename: Sérgio Danilo Junho
authors.initials: SD
authors.lastname: Pena
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Poupon
authors.forename: Thomas
authors.initials: T
authors.lastname: Helleday
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tagawa
authors.forename: Carlosrenato
authors.initials: C
authors.lastname: Machado
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hoffmann
authors.forename: Christophe
authors.initials: C
authors.lastname: Cazaux
mesh_terms: D000782:Aneuploidy; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002874:Chromosome Mapping; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D005787:Gene Frequency; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D011995:Recombination, Genetic; D000099270:Y-Family DNA Polymerases
chemical_list: D004259:DNA-Directed DNA Polymerase; C404302:POLK protein, human; D000099270:Y-Family DNA Polymerases