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: 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, Carlosrenato Machado, Jean-Sébastien Hoffmann, Christophe Cazaux
• Journal: Cancer research (Cancer Res) Vol. 65 Issue 1 Pg. 325-30 (Jan 01 2005) ISSN: 0008-5472 [Print] United States
• PMID: 15665310 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Directed DNA Polymerase
• POLK protein, human

Topics

• 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