title: Sublimiting concentration of TFIIH transcription/DNA repair factor causes TTD-A trichothiodystrophy disorder.
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.
authors.affiliation: Department of Cell Biology and Genetics, Medical Genetics Center, Erasmus University Rotterdam, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Vermeulen
authors.forename: E
authors.initials: E
authors.lastname: Bergmann
authors.forename: J
authors.initials: J
authors.lastname: Auriol
authors.forename: S
authors.initials: S
authors.lastname: Rademakers
authors.forename: P
authors.initials: P
authors.lastname: Frit
authors.forename: E
authors.initials: E
authors.lastname: Appeldoorn
authors.forename: J H
authors.initials: JH
authors.lastname: Hoeijmakers
authors.forename: J M
authors.initials: JM
authors.lastname: Egly
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002461:Cell Line, Transformed; D003057:Cockayne Syndrome / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004249:DNA Damage; D004265:DNA Helicases / Q000172:deficiency / Q000235:genetics; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005816:Genetic Complementation Test; D018740:Genetic Heterogeneity; D006201:Hair Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D009097:Multienzyme Complexes / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D046988:Proteasome Endopeptidase Complex; D021122:Protein Subunits; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D012871:Skin Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013577:Syndrome; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000737:chemistry / Q000172:deficiency / Q000502:physiology*; D019473:Transcription Factors, TFII; D014158:Transcription, Genetic; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000473:pathology; D051759:Xeroderma Pigmentosum Group D Protein
chemical_list: D004268:DNA-Binding Proteins; C095472:ERCC8 protein, human; D046911:Macromolecular Substances; D009097:Multienzyme Complexes; D000075223:Poly-ADP-Ribose Binding Proteins; D021122:Protein Subunits; D011506:Proteins; D014157:Transcription Factors; D019473:Transcription Factors, TFII; C072022:XPBC-ERCC-3 protein; D051758:Transcription Factor TFIIH; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D004265:DNA Helicases; C078673:ERCC6 protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D045643:DNA Repair Enzymes