Abnormal regulation of DDB2 gene expression in xeroderma pigmentosum group E strains

Oncogene. 2001 Oct 25;20(48):7041-50. doi: 10.1038/sj.onc.1204909.


A damage-specific DNA binding protein (DDB) activity is absent from a subset (DDB(-)) of cells from individuals initially classified as group E of xeroderma pigmentosum (XP), a hereditary, photosensitive disease with a high incidence of skin malignancies. In these cases, mutations have been identified in the DDB2 gene (DDB2(-)) that codes for the small subunit, p48, of the DDB heterodimer. In four DDB2(- )strains, neither p48 nor DDB activity were observed before or after UV-irradiation, despite an unusually strong up-regulation of DDB2 mRNA levels after UV-irradiation. In a fifth strain, XP82TO, p48 was detectable and both DDB2 mRNA and p48 levels were more up-regulated after UV-irradiation than in normal primary cells. Moreover, DDB activity also became apparent after irradiation. XP82TO showed very mild clinical manifestations compared with the other DDB(-) patients. These results, coupled with our findings that most, if not all DDB(+) cells classified as XP-E were misclassified, suggests a direct correlation between DDB2 levels and the XP-E phenotype.

Publication types

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

MeSH terms

  • Cells, Cultured / metabolism
  • Cells, Cultured / radiation effects
  • Cellular Senescence
  • DNA / biosynthesis
  • DNA / radiation effects
  • DNA Damage
  • DNA Repair / genetics
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / genetics
  • Dimerization
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibroblasts / radiation effects
  • Gene Expression Regulation / radiation effects*
  • Genetic Predisposition to Disease
  • Humans
  • Neoplasms, Radiation-Induced / genetics
  • Neoplastic Syndromes, Hereditary / genetics
  • Osteosarcoma / pathology
  • Phenotype
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Tumor Cells, Cultured
  • Ultraviolet Rays
  • Xeroderma Pigmentosum / classification
  • Xeroderma Pigmentosum / genetics*
  • Xeroderma Pigmentosum / metabolism
  • Xeroderma Pigmentosum / pathology


  • DDB2 protein, human
  • DNA-Binding Proteins
  • RNA, Messenger
  • DNA