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2
* Groupe ‘Instabilité génétique et cancer’,
Groupe ‘Toxico-résistance’, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 31077 Toulouse cedex 4, France; and
Department of Biochemistry, Medical school of Kyushu University, Fukuoka 812-8582, Japan
2Correspondence: Groupe ‘Instabilité génétique et cancer’, Groupe ‘Toxico-résistance’, Institut de Pharmacologie et de Biologie Structurale, CNRS UPR 9062, 205 route de Narbonne, 31077 Toulouse cedex 4, France. E-mail: cazaux@ipbs.fr; salles{at}ipbs.fr
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 
and/or 
participate to the repair DNA
synthesis step. Using UV and cisplatin-modified DNA templates, we
measured in vitro that extracts from cells
overexpressing the error-prone DNA polymerase ß exhibited a five- to
sixfold increase of the ultimate DNA synthesis activity compared with
control extracts and demonstrated the specific involvement of Pol ß
in this step. By using a 28 nt gapped, double-stranded DNA substrate
mimicking the product of the incision step, we showed that Pol ß 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 ß 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 ß: a potential source of genetic
instability in cancer cells.
Key Words: cell variants • DNA repair • mutagenesis
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