Up-regulation of the error-prone DNA polymerase κ promotes pleiotropic genetic alterations and tumorigenesis

Clarisse Bavoux, Andréia Machado Leopoldino, Valérie Bergoglio, Jiyang O-Wang, Tomoo Ogi, Anne Bieth, Jean Gabriel Judde, Sérgio Danilo Junho Pena, Marie France Poupon, Thomas Helleday, Masatoshi Tagawa, Carlos Renato Machado, Jean Sébastien Hoffmann, Christophe Cazaux

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

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 κ, 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 κ, 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.

Original languageEnglish
Pages (from-to)325-330
Number of pages6
JournalCancer Research
Volume65
Issue number1
StatePublished - 1 Jan 2005
Externally publishedYes

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