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.