Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Abnormalities, Multiple / genetics*
-
Cell Line, Transformed
-
Cockayne Syndrome / genetics
-
Cysteine Endopeptidases / metabolism
-
DNA Damage
-
DNA Helicases / deficiency
-
DNA Helicases / genetics
-
DNA Repair Enzymes
-
DNA Repair*
-
DNA-Binding Proteins / chemistry
-
DNA-Binding Proteins / deficiency
-
DNA-Binding Proteins / genetics
-
Fibroblasts / metabolism
-
Fibroblasts / pathology
-
Genetic Complementation Test
-
Genetic Heterogeneity
-
Hair Diseases / genetics*
-
Hair Diseases / metabolism
-
Hair Diseases / pathology
-
HeLa Cells
-
Humans
-
Macromolecular Substances
-
Multienzyme Complexes / metabolism
-
Poly-ADP-Ribose Binding Proteins
-
Proteasome Endopeptidase Complex
-
Protein Subunits
-
Proteins / chemistry
-
Proteins / genetics
-
Skin Diseases / genetics*
-
Skin Diseases / metabolism
-
Skin Diseases / pathology
-
Syndrome
-
Transcription Factor TFIIH
-
Transcription Factors / chemistry
-
Transcription Factors / deficiency
-
Transcription Factors / physiology*
-
Transcription Factors, TFII*
-
Transcription, Genetic*
-
Xeroderma Pigmentosum / genetics
-
Xeroderma Pigmentosum / pathology
-
Xeroderma Pigmentosum Group D Protein
Substances
-
DNA-Binding Proteins
-
ERCC8 protein, human
-
Macromolecular Substances
-
Multienzyme Complexes
-
Poly-ADP-Ribose Binding Proteins
-
Protein Subunits
-
Proteins
-
Transcription Factors
-
Transcription Factors, TFII
-
XPBC-ERCC-3 protein
-
Transcription Factor TFIIH
-
Cysteine Endopeptidases
-
Proteasome Endopeptidase Complex
-
DNA Helicases
-
ERCC6 protein, human
-
Xeroderma Pigmentosum Group D Protein
-
ERCC2 protein, human
-
DNA Repair Enzymes