title: Abnormal regulation of DDB2 gene expression in xeroderma pigmentosum group E strains.
abstract: 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.
authors.affiliation: Division of Biochemistry and Molecular Biology, 229 Stanley Hall, University of California, Berkeley, California, CA 94720-3206, USA.
authors.forename: T
authors.initials: T
authors.lastname: Itoh
authors.forename: A
authors.initials: A
authors.lastname: Nichols
authors.forename: S
authors.initials: S
authors.lastname: Linn
mesh_terms: D002478:Cells, Cultured / Q000378:metabolism / Q000528:radiation effects; D016922:Cellular Senescence; D004247:DNA / Q000096:biosynthesis / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D019281:Dimerization; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009381:Neoplasms, Radiation-Induced / Q000235:genetics; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics; D012516:Osteosarcoma / Q000473:pathology; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D004247:DNA