Sublimiting concentration of TFIIH transcription/DNA repair factor causes TTD-A trichothiodystrophy disorder

The repair-deficient form of trichothiodystrophy (TTD) most often results f rom mutations in the genes XPB or XPD. encoding helicases of the transcript ion/repair factor TFIIH. The genetic defect in a third group, TTD-A, is unk nown, but is also caused by dysfunctioning TFIIH. None of the TFIIH subunit s carry a mutation and TFIIH from fro-A cells is active in both transcripti on and repair. Instead, immunoblot and immunofluorescence analyses reveal a strong reduction in the TFIIH concentration. Thus, the phenotype of TTD-A appears to result from sublimiting amounts of TFIIH, probably due to a muta tion in a gene determining the complex stability. The reduction of TFIIH ma inly affects its repair function and hardly influences transcription.