A new, tenth subunit TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A

Giuseppina Giglia-Mari, Frederic Coin, Jeffrey A. Ranish, Deborah Hoogstraten, Arjan Theil, Nils Wijgers, Nicolaas G.J. Jaspers, Anja Raams, Manuela Argentini, P. J. Van Der Spek, Elena Botta, Miria Stefanini, Jean Marc Egly, Ruedi Aebersold, Jan H.J. Hoeijmakers, Wim Vermeulen

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

282 Citaten (Scopus)

Samenvatting

DNA repair-deficient trichothiodystrophy (TTD) results from mutations in the XPD and XPB subunits of the DNA repair and transcription factor TFIIH. In a third form of DNA repair-deficient TTD, called group A, none of the nine subunits encoding TFIIH carried mutations; instead, the steady-state level of the entire complex was severely reduced1. A new, tenth TFIIH subunit (TFB5) was recently identified in yeast2. Here, we describe the identification of the human TFB5 ortholog and its association with human TFIIH. Microinjection of cDNA encoding TFB5 (GTF2H5, also called TTDA) corrected the DNA-repair defect of TTD-A cells, and we identified three functional inactivating mutations in this gene in three unrelated families with TTD-A. The GTF2H5 gene product has a role in regulating the level of TFIIH. The identification of a new evolutionarily conserved subunit of TFIIH implicated in TTD-A provides insight into TFIIH function in transcription, DNA repair and human disease.

Originele taal-2Engels
Pagina's (van-tot)714-719
Aantal pagina's6
TijdschriftNature Genetics
Volume36
Nummer van het tijdschrift7
DOI's
StatusGepubliceerd - jul. 2004
Extern gepubliceerdJa

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