Overexpression of DNA polymerase beta: a genomic instability enhancer process

DNA polymerase beta (Pol beta) is the most inaccurate of the six DNA polyme rases 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 syn thesis in the base excision repair pathway participating to the genome stab ility. However, excess of Pol beta, found in some human tumors, could confe r an increase in spontaneous mutagenesis and result in a highly mutagenic t olerance phenotype toward bifunctional DNA crosslinking anticancer drugs, H ere, we present a hypothesis on the mechanisms used by Pol beta to be a gen etic instability enhancer through its overexpression, We hypothesize that a n excess of pol beta perturbs the well-defined specific functions of DNA po lymerases 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 mutagen ic base analogs like those produced by intracellular oxidative processes. T hese mechanisms may predominate during cellular nonproliferative phases in the absence of DNA replication.