Sublimiting concentration of TFIIH transcription/DNA repair factor causes TTD-A trichothiodystrophy disorder.
The repair-deficient form of trichothiodystrophy (TTD) most often results from mutations in the genes XPB or XPD, encoding helicases of the transcription/repair factor TFIIH. The genetic defect in a third group, TTD-A, is unknown, but is also caused by dysfunctioning TFIIH. None of the TFIIH subunits carry a mutation and TFIIH from TTD-A cells is active in both transcription 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 mutation in a gene determining the complex stability. The reduction of TFIIH mainly affects its repair function and hardly influences transcription.
Pubmed ID: 11062469 RIS Download
Abnormalities, Multiple | Cell Line, Transformed | Cockayne Syndrome | Cysteine Endopeptidases | DNA Damage | DNA Helicases | DNA Repair | DNA Repair Enzymes | DNA-Binding Proteins | Fibroblasts | Genetic Complementation Test | Genetic Heterogeneity | Hair Diseases | HeLa Cells | Humans | Macromolecular Substances | Multienzyme Complexes | Proteasome Endopeptidase Complex | Protein Subunits | Proteins | Skin Diseases | Syndrome | Transcription Factor TFIIH | Transcription Factors | Transcription Factors, TFII | Transcription, Genetic | Xeroderma Pigmentosum | Xeroderma Pigmentosum Group D Protein