TY - JOUR
T1 - A new, tenth subunit TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A
AU - Giglia-Mari, Giuseppina
AU - Coin, Frederic
AU - Ranish, Jeffrey A.
AU - Hoogstraten, Deborah
AU - Theil, Arjan
AU - Wijgers, Nils
AU - Jaspers, Nicolaas G.J.
AU - Raams, Anja
AU - Argentini, Manuela
AU - Van Der Spek, P. J.
AU - Botta, Elena
AU - Stefanini, Miria
AU - Egly, Jean Marc
AU - Aebersold, Ruedi
AU - Hoeijmakers, Jan H.J.
AU - Vermeulen, Wim
PY - 2004/7
Y1 - 2004/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=3042781670&partnerID=8YFLogxK
U2 - 10.1038/ng1387
DO - 10.1038/ng1387
M3 - Article
C2 - 15220921
AN - SCOPUS:3042781670
SN - 1061-4036
VL - 36
SP - 714
EP - 719
JO - Nature Genetics
JF - Nature Genetics
IS - 7
ER -