Nature Genetics
36, 714 - 719 (2004)
Published online: 27 June 2004; | doi:10.1038/ng1387
A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group AGiuseppina Giglia-Mari1, Frederic Coin2, Jeffrey A Ranish3, Deborah Hoogstraten1, Arjan Theil1, Nils Wijgers1, Nicolaas G J Jaspers1, Anja Raams1, Manuela Argentini2, P J van der Spek4, Elena Botta5, Miria Stefanini5, Jean-Marc Egly2, Ruedi Aebersold3, Jan H J Hoeijmakers1
& Wim Vermeulen11
Department of Genetics, Medical Genetic Cluster, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. 2
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France. 3
Institute for Systems Biology, Seattle, Washington, USA. 4
Department of Bioinformatics, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. 5
Istituto di Genetica Biochimica ed Evoluzionistica, CNR, Pavia, Italy.
Correspondence should be addressed to Wim Vermeulen w.vermeulen@erasmusmc.nlDNA 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.
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