Structure, function and evolution of the XPD family of iron-sulfur- containing 5'→3' DNA helicases

Malcolm F. White*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)


The XPD (xeroderma pigmentosum complementation group D) helicase family comprises a number of superfamily 2 DNA helicases with members found in all three domains of life. The founding member, the XPD helicase, is conserved in archaea and eukaryotes, whereas the closest homologue in bacteria is the DinG (damage-inducible G) helicase. Three XPD paralogues, FancJ (Fanconi's anaemia complementation group J), RTEL (regular of telomere length) and Chl1, have evolved in eukaryotes and function in a variety of DNA recombination and repair pathways. All family members are believed to be 5'→3' DNA helicases with a structure that includes an essential iron-sulfur-cluster-binding domain. Recent structural, mutational and biophysical studies have provided a molecular framework for the mechanism of the XPD helicase and help to explain the phenotypes of a considerable number of mutations in the XPD gene that can cause three different genetic conditions: xeroderma pigmentosum, trichothiodystrophy and Cockayne's syndrome. Crystal structures of XPD from three archaeal organisms reveal a four-domain structure with two canonical motor domains and two unique domains, termed the Arch and iron-sulfur-cluster-binding domains. The latter two domains probably collaborate to separate duplex DNA during helicase action. The role of the iron-sulfur cluster and the evolution of the XPD helicase family are discussed.

Original languageEnglish
Pages (from-to)547-551
Number of pages5
JournalBiochemical Society Symposium
Publication statusPublished - 1 Dec 2009


  • Archaeon
  • Fanconi's anaemia complementation group J (FancJ)
  • Helicase
  • Iron-sulfur-cluster-binding domain
  • Molecular evolution
  • Xeroderma pigmentosum complementation group D (XPD)


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