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IPBS - CNRS UPR 9062, groupe Instabilité Génétique et Cancer, 31077 Toulouse cedex, France
1Correspondence: Jean-Sébastien Hoffmann (jseb@ipbs.fr) and Christophe Cazaux, IPBS - CNRS UPR 9062, groupe Instabilité Génétique et Cancer, 205 route de Narbonne, 31077 Toulouse cedex, France.
DNA polymerase ß (Pol ß) is the most inaccurate of the six DNA polymerases found in mammalian cells. In a normal situation, it is expressed at a constant low level and its role is believed to be restricted to repair synthesis in the base excision repair pathway participating to the genome stability. However, excess of Pol ß, found in some human tumors, could confer an increase in spontaneous mutagenesis and result in a highly mutagenic tolerance phenotype toward bifunctional DNA cross-linking anticancer drugs. Here, we present a hypothesis on the mechanisms used by Pol ß to be a genetic instability enhancer through its overexpression. We hypothesize that an excess of Pol ß perturbs the well-defined specific functions of DNA polymerases developed by the cell and propose Pol ß-mediated gap fillings during DNA transactions like repair, replication, or recombination pathways as key processes to introduce illegitimate deoxyribonucleotides or mutagenic base analogs like those produced by intracellular oxidative processes. These mechanisms may predominate during cellular nonproliferative phases in the absence of DNA replication.—Canitrot, Y., Fréchet, M., Servant, L., Cazaux, C., Hoffmann, J.-S. Overexpression of DNA polymerase ß: a genomic instability enhancer process.
Key Words: DNA replication • Pol ß • mismatch repair • nucleotide excision repair
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