Trichothiodystrophy (TTD) is a rare genetic disease with heterogeneous clinical features associated with specific deficiencies in nucleotide excision repair. Patients have brittle hair due to a reduced content of cysteine-rich matrix proteins. About 50% of the cases reported in the literature are photosensitive. In these patients an altered cellular response to UV, due to a specific deficiency in nucleotide excision repair, has been observed. The majority of repair-defective TTD patients have been assigned by complementation analysis to group D of xeroderma pigmentosum (XP). Recently, the human excision repair gene ERCC2 has been shown to correct the UV sensitivity of XP-D fibroblasts. In this work we describe the effect of ERCC2 on the DNA repair deficient phenotype of XP-D and on two repair-defective TTD cell strains (TTD1VI and TTD2VI) assigned by complementation analysis to group D of XP. ERCC2 cDNA, cloned into a mammalian expression vector, was introduced into TTD and XP fibroblasts via DNA-mediated transfection or microneedle injection. UV sensitivity and cellular DNA repair properties, including unscheduled DNA synthesis and reactivation of a UV-irradiated plasmid containing the chloramphenicol acetyltransferase reporter gene (pRSVCat), were corrected to wild-type levels in both TTD and XP-D cells. These data show that a functional ERCC2 gene is sufficient to reestablish a wild-type DNA repair phenotype in TTD1VI and TTD2VI cells, confirming the genetic relationship between TTD and XP-D. Furthermore, our findings suggest that mutations at the ERCC2 locus are responsible for causing a similar phenotype in TTD and XP-D cells in response to UV irradiation, but produce quite different clinical symptoms.

Additional Metadata
Keywords *DNA Repair, *Radiation Tolerance, *Ultraviolet Rays, 0 (Proteins), 130067-74-2 (ERCC-2 protein), Animals, Cell Line, Cell Survival/radiation effects, Female, Hair Diseases/*genetics, Hamsters, Human, Phenotype, Proteins/*genetics, Support, Non-U.S. Gov't, Xeroderma Pigmentosum/*genetics
Persistent URL hdl.handle.net/1765/3059
Citation
Mezzina, M., Eveno, E., Chevalier-Lagente, O., Benoit, A., Carreau, M., Vermeulen, W., … Sarasin, A.. (1994). Correction by the ERCC2 gene of UV sensitivity and repair deficiency phenotype in a subset of trichothiodystrophy cells.. Carcinogenesis: integrative cancer research, 15, 1493–1498. Retrieved from http://hdl.handle.net/1765/3059