Overexpression of DNA polymerase beta: a genomic instability enhancer process.
DNA polymerase beta (Pol beta) 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 beta, 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 beta to be a genetic instability enhancer through its overexpression. We hypothesize that an excess of Pol beta perturbs the well-defined specific functions of DNA polymerases developed by the cell and propose Pol beta-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
Y
IPBS - CNRS UPR 9062, groupe Instabilité Génétique et Cancer, 31077 Toulouse cedex, France.
Frechet
M
M
Servant
L
L
Cazaux
C
C
Hoffmann
J S
JS
D019951:DNA Polymerase beta / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D016296:Mutagenesis; D009369:Neoplasms / Q000235:genetics
D019951:DNA Polymerase beta; D004259:DNA-Directed DNA Polymerase