Human xeroderma pigmentosum group D gene encodes a DNA helicase

Nature. 1993 Oct 28;365(6449):852-5. doi: 10.1038/365852a0.

Abstract

Xeroderma pigmentosum (XP), a genetically heterogeneous human disease, results from a defect in nucleotide excision repair of ultraviolet-damaged DNA. XP patients are extremely sensitive to sunlight and suffer from a high incidence of skin cancers. Cell fusion studies have identified seven XP complementation groups, A-G. Group D is of particular interest as mutations in this gene can also cause Cockayne's syndrome and trichothiodystrophy. The XPD gene was initially named ERCC2 (excision repair cross complementing) as it was cloned using human DNA to complement the ultraviolet sensitivity of a rodent cell line. We have purified the XPD protein to near homogeneity and show that it possesses single-stranded DNA-dependent ATPase and DNA helicase activities. We tested whether XPD can substitute for its yeast counterpart RAD3, which is essential for excision repair and for cell viability. Expression of the XPD gene in Saccharomyces cerevisiae can complement the lethality defect of a mutation in the RAD3 gene, suggesting that XPD is an essential gene in humans.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphate / metabolism
  • Bacteriophage M13
  • Bacteriophage phi X 174
  • Cloning, Molecular
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • DNA Repair
  • DNA, Single-Stranded / metabolism
  • DNA, Viral / metabolism
  • DNA-Binding Proteins*
  • Escherichia coli
  • Genetic Complementation Test
  • Humans
  • Proteins / genetics*
  • Proteins / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors*
  • Xeroderma Pigmentosum / enzymology
  • Xeroderma Pigmentosum / genetics*
  • Xeroderma Pigmentosum Group D Protein

Substances

  • DNA, Single-Stranded
  • DNA, Viral
  • DNA-Binding Proteins
  • Proteins
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • Rad3 protein, S cerevisiae
  • DNA Helicases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human