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

Bavoux, C., Leopoldino, A. M., Bergoglio, V., J, O. Wang, Ogi, T., Bieth, A., Judde, J. G., Pena, S. D., Poupon, M. F., Helleday, T., Tagawa, M., Machado, C., Hoffmann, J. S. and Cazaux, C. (2005) Up-regulation of the error-prone DNA polymerase {kappa} promotes pleiotropic genetic alterations and tumorigenesis. Cancer Research, 65 (1). pp. 325-30. ISSN 0008-5472

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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.

Item Type: Article
Additional Information: 0008-5472 Journal Article GDSC137
Keywords: 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 Research Support, Non-U.S. Gov't
Depositing User: Gee Wheatley
Date Deposited: 19 Mar 2007
Last Modified: 12 Jun 2012 14:28
URI: http://sro.sussex.ac.uk/id/eprint/963
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