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Recovery of Normal DNA Repair and Mutagenesis in Trichothiodystrophy Cells after Transduction of the XPD Human Gene¹

Laboratory of Molecular Genetics, UPR 42 Centre National de la Recherche Scientifique IFC1, Institut de Recherches sur le Cancer, BP8-94801 Villejuif, France

To determine whether expression of the XPD/ERCC2 repair gene in trichothiodystrophy (TTD) group D cells could restore mutagenesis characteristics of repair-proficient cells, we compared the UV mutagenesis of normal cells, TTD group D cells, and TTD group D cells retrovirally transduced by the wild-type XPD/ERCC2 gene (TTD + ERCC2 cells). We first verified the expression of the XPD protein, correction of UV cell survival, and DNA repair ability of TTD + ERCC2 cells. UV-induced mutations were studied using the pR2 shuttle vector. The addition of the XPD/ERCC2 gene in TTD cells led to a significant but partial decrease of mutation frequency compared with the parental TTD cells. Types of mutations of TTD + ERCC2 cells get closer to those observed in normal cells (i.e., a reduction of multiple mutations). New hotspots appeared and some disappeared in the complemented line, suggesting that hospot distribution is particular to each cell line and cannot be correlated with the repair status of the cells. In conclusion, the expression of the XPD/ERCC2 repair gene completely corrected UV hypersensitivity and almost all types of mutations of TTD group D cells, whereas hypermutagenesis was partially corrected.

¹ This work was supported by the Ligue Française Nationale Contre le Cancer, the Fondation de France, and the Association Française contre les Myopathies (Paris, France). C. M. held a fellowship from the Centre National de la Recherche Scientifique (Paris, France), and X. Q. held a fellowship from the Institut de Formation Supérieure Bio-Médicale (Villejuif, France).

² To whom requests for reprints should be addressed. Phone: 33-1-49 58 34 20; Fax: 33-1-49 58 34 43.

Received 5/ 7/96. Accepted 10/ 3/96.

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