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

Wim Vermeulen, Etienne Bergmann, Jérôme Auriol, Suzanne Rademakers, Philippe Frit, Esther Appeldoorn, Jan H.J. Hoeijmakers, Jean Marc Egly

Research output: Contribution to journalArticlepeer-review

109 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)307-313
Number of pages7
JournalNature Genetics
Volume26
Issue number3
DOIs
Publication statusPublished - 2000
Externally publishedYes

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