Up-regulation of the error-prone DNA polymerase {kappa} promotes pleiotropic genetic alterations and tumorigenesis

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...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2005-01, Vol.65 (1), p.325-330
Main Authors: Bavoux, Clarisse, Leopoldino, Andréia Machado, Bergoglio, Valérie, O-Wang, Jiyang, Ogi, Tomoo, Bieth, Anne, Judde, Jean-Gabriel, Pena, Sérgio Danilo Junho, Poupon, Marie-France, Helleday, Thomas, Tagawa, Masatoshi, Machado, Carlosrenato, Hoffmann, Jean-Sébastien, Cazaux, Christophe
Format: Article
Language:English
Subjects:
Aneuploidy
Cell Line
Cell Transformation, Neoplastic - genetics
Chromosome Mapping
DNA-Directed DNA Polymerase - genetics
Gene Expression Regulation, Enzymologic - genetics
Gene Frequency
Genomic Instability - genetics
Humans
Mutation
Neoplasms - genetics
Recombination, Genetic
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Summary: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.
ISSN:0008-5472