Nucleotide excision repair DNA synthesis by excess DNA polymerase β: a potential source of genetic instability in cancer cells

The nucleotide excision repair pathway contributes to genetic stability by removing a wide range of DNA damage through an error‐free reaction. When the lesion is located, the altered strand is incised on both sides of the lesion and a damaged oligonucleotide excised. A repair patch is then synthesized and the repaired strand is ligated. It is assumed that only DNA polymerases δ and/or ε participate to the repair DNA synthesis step. Using UV and cisplatin‐modified DNA templates, we measured in vitrothat extracts from cells overexpressing the error‐prone DNA polymerase β exhibited a five‐to sixfold increase of the ultimate DNA synthesis activity compared with control extracts and demonstrated the specific involvement of Pol β in this step. By using a 28 nt gapped, double‐stranded DNA substrate mimicking the product of the incision step, we showed that Pol β is able to catalyze strand displacement downstream of the gap. We discuss these data within the scope of a hypothesis previously presented proposing that excess error‐prone Pol β in cancer cells could perturb the well‐defined specific functions of DNA polymerases during error‐free DNA transactions.—Canitrot, Y., Hoffmann, J.‐S., Calsou, P., Hayakawa, H., Salles, B., Cazaux, C. Nucleotide excision repair DNA synthesis by excess DNA polymerase β: a potential source of genetic instability in cancer cells. FASEB J.14, 1765–1774 (2000)