A NEW NUCLEOTIDE-EXCISION-REPAIR GENE ASSOCIATED WITH THE DISORDER TRICHOTHIODYSTROPHY

The sun-sensitive, cancer-prone genetic disorder xeroderma pigmentosum (XP) is associated in most cases with a defect in the ability to carr y out excision repair of UV damage. Seven genetically distinct complem entation groups (i.e., A-G) have been identified. A large proportion o f patients with the unrelated disorder trichothiodystrophy (TTD), whic h is characterized by hair-shaft abnormalities, as well as by physical and mental retardation, are also deficient in excision repair of UV d amage. In most of these cases the repair deficiency is in the same com plementation group as is XP group D. We report here on cells from a pa tient, TTD1BR, in which the repair defect complements all known XP gro ups (including XP-D). Furthermore, microinjection of various cloned hu man repair genes fails to correct the repair defect in this cell strai n. The defect in TTD1BR cells is therefore in a new gene involved in e xcision repair in human cells. The finding of a second DNA repair gene that is associated with the clinical features of TTD argues strongly for an involvement of repair proteins in hair-shaft development.