Mutations in the XPD Helicase Gene Result in XP and TTD Phenotypes, Preventing Interaction Between XPD and the p44 Subunit of TFIIH

Nat Genet. 1998 Oct;20(2):184-8. doi: 10.1038/2491.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • DNA Repair*
  • DNA-Binding Proteins*
  • Hair Diseases / genetics*
  • Humans
  • Mutation
  • Protein Conformation
  • Proteins / genetics*
  • Proteins / metabolism
  • Transcription Factor TFIIH
  • Transcription Factors / metabolism*
  • Transcription Factors, TFII*
  • Xeroderma Pigmentosum / genetics*
  • Xeroderma Pigmentosum Group D Protein

Substances

  • DNA-Binding Proteins
  • Proteins
  • Transcription Factors
  • Transcription Factors, TFII
  • Transcription Factor TFIIH
  • DNA Helicases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human