Reinvestigation of the classification of five cell strains of xeroderma pigmentosum group E with reclassification of three of them.
Xeroderma pigmentosum is a photosensitive syndrome caused by a defect in nucleotide excision repair or postreplication repair. Individuals of xeroderma pigmentosum group E (xeroderma pigmentosum E) have a mild clinical form of the disease and their cells exhibit a high level of nucleotide excision repair as measured by unscheduled DNA synthesis, as well as biochemical heterogeneity. Cell strains from one group of xeroderma pigmentosum E patients have normal damage-specific DNA binding activity (Ddb+), whereas others do not (Ddb-). Using a refinement of a previously reported cell fusion complementation assay, the previously assigned Ddb+ xeroderma pigmentosum E strains, XP89TO, XP43TO, and XP24KO, with various phenotypes in DNA repair markers, were reassigned to xeroderma pigmentosum group F, xeroderma pigmentosum variant, and ultraviolet-sensitive syndrome, respectively. The Ddb- xeroderma pigmentosum E strains, XP82TO, and GM02415B, which showed almost normal cellular phenotypes in DNA repair markers, however, remained assigned to xeroderma pigmentosum group E. With the exception of the Ddb+ strain XP89TO, which demonstrated defective nucleotide excision repair, both Ddb- and Ddb+ xeroderma pigmentosum E cells exhibited the same levels of variation in unscheduled DNA synthesis that were seen in normal control cells. By genome DNA sequencing, the two Ddb- xeroderma pigmentosum E strains were shown to have mutations in the DDB2 gene, confirming previous reports for XP82TO and GM02415B, and validating the classification of both cells. As only the Ddb- strains investigated remain classified in the xeroderma pigmentosum E complementation group, it is feasible that only Ddb- cells are xeroderma pigmentosum E and that mutations in the DDB2 gene are solely responsible for the xeroderma pigmentosum E group.
Itoh
T
T
Department of Cell Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto, Japan. toshiki@uclink4.berkeley.edu
Linn
S
S
Ono
T
T
Yamaizumi
M
M
D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D009154:Mutation; D011836:Radiation Tolerance; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000473:pathology*
C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D004247:DNA