Abnormal XPD-induced nuclear receptor transactivation in DNA repair disorders: Trichothiodystrophy and xeroderma pigmentosum

Xiaolong Zhou, Sikandar G. Khan, Deborah Tamura, Takahiro Ueda, Jennifer Boyle, Emmanuel Compe, Jean Marc Egly, John J. Digiovanna, Kenneth H. Kraemer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


XPD (ERCC2) is a DNA helicase involved in nucleotide excision repair and in transcription as a structural bridge tying the transcription factor IIH (TFIIH) core with the cdk-activating kinase complex, which phosphorylates nuclear receptors. Mutations in XPD are associated with several different phenotypes, including trichothiodystrophy (TTD), with sulfur-deficient brittle hair, bone defects, and developmental abnormalities without skin cancer, xeroderma pigmentosum (XP), with pigmentary abnormalities and increased skin cancer, or XP/TTD with combined features, including skin cancer. We describe the varied clinical features and mutations in nine patients examined at the National Institutes of Health who were compound heterozygotes for XPD mutations but had different clinical phenotypes: four TTD, three XP, and two combined XP/TTD. We studied TFIIH-dependent transactivation by nuclear receptor for vitamin D (VDR) and thyroid in cells from these patients. The vitamin D stimulation ratio of CYP24 and osteopontin was associated with specific pairs of mutations (reduced in 5, elevated in 1) but not correlated with distinct clinical phenotypes. Thyroid receptor stimulation ratio for KLF9 was not significantly different from normal. XPD mutations frequently were associated with abnormal VDR stimulation in compound heterozygote patients with TTD, XP, or XP/TTD.

Original languageEnglish (US)
Pages (from-to)831-837
Number of pages7
JournalEuropean Journal of Human Genetics
Issue number8
StatePublished - Aug 2013


  • DNA repair
  • Human development
  • Transcription
  • Vitamin D receptor

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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