Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH.
In most cases, xeroderma pigmentosum group D (XP-D) and trichothiodystrophy (TTD) patients carry mutations in the carboxy-terminal domain of the evolutionarily conserved helicase XPD, which is one of the subunits of the transcription/repair factor TFIIH (refs 1,2). In this study, we demonstrate that XPD interacts specifically with p44, another subunit of TFIIH, and that this interaction results in the stimulation of 5'-->3' helicase activity. Mutations in the XPD C-terminal domain, as found in most patients, prevent the interaction with p44, thus explaining the decrease in XPD helicase activity and the nucleotide excision repair (NER) defect.
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P.163, Illkirch, C.U. de Strasbourg, France.
F
F
Coin
J C
JC
Marinoni
C
C
Rodolfo
S
S
Fribourg
A M
AM
Pedrini
J M
JM
Egly
D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins; D006201:Hair Diseases / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011487:Protein Conformation; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism*; D019473:Transcription Factors, TFII; D014983:Xeroderma Pigmentosum / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein
D004268:DNA-Binding Proteins; D011506:Proteins; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D051758:Transcription Factor TFIIH; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human