title: A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A.
abstract: 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 reduced. A new, tenth TFIIH subunit (TFB5) was recently identified in yeast. 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.
authors.affiliation: Department of Genetics, Medical Genetic Cluster, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Giglia-Mari
authors.forename: Frederic
authors.initials: F
authors.lastname: Coin
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Ranish
authors.forename: Deborah
authors.initials: D
authors.lastname: Hoogstraten
authors.forename: Arjan
authors.initials: A
authors.lastname: Theil
authors.forename: Nils
authors.initials: N
authors.lastname: Wijgers
authors.forename: Nicolaas G J
authors.initials: NG
authors.lastname: Jaspers
authors.forename: Anja
authors.initials: A
authors.lastname: Raams
authors.forename: Manuela
authors.initials: M
authors.lastname: Argentini
authors.forename: P J
authors.initials: PJ
authors.lastname: van der Spek
authors.forename: Elena
authors.initials: E
authors.lastname: Botta
authors.forename: Miria
authors.initials: M
authors.lastname: Stefanini
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Egly
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.forename: Jan H J
authors.initials: JH
authors.lastname: Hoeijmakers
authors.forename: Wim
authors.initials: W
authors.lastname: Vermeulen
mesh_terms: D004260:DNA Repair; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells; D006801:Humans; D008845:Microinjections; D016366:Open Reading Frames; D051758:Transcription Factor TFIIH; D019473:Transcription Factors, TFII / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D019473:Transcription Factors, TFII; D051758:Transcription Factor TFIIH