Abstract
The major DNA damage induced by solar UV is cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts (6-4PP) formed between adjacent pyrimidines. These damage plays significant roles in cell killing, mutation and neoplastic transformation, and is repaired by nucleotide excision repair (NER), the only pathway in human. NER needs more than 30 different proteins for the process including damage recognition, removal of the oligonucleotides containing the damage, gap-filling DNA synthesis, and ligation. Defects in NER are associated with autosomal diseases, xeroderma pigmentosum (XP), Cockayne syndrome, and trichothiodystrophy (TTD). TTD is characterized by brittle hair with reduced sulfur content, ichthyosis, and impaired mental and physical development. The photosensitive form of TTD results from mutations in the same XPD gene as the cancer-prone XP group D (XP-D). Nevertheless, no increase in skin cancers appears in patients with TTD. In this study, we asked whether the cancer-free phenotype in TTD is related to its repair defect. We found that all three TTD cell strains are deficient in the repair of both CPD and 6-4PP. UV sensitivity correlated well with the severity of repair defects. Moreover, mutations of the XPD gene affected both the recruitment of the TFIIH complex to DNA damage sites and the TFIIH expression. The present results indicate that there is no major difference in the repair defect between TTD and XP-D and that the cancer-free phenotype is unrelated to a DNA repair defect.
