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 nu cleotide excision repair or postreplication repair. Individuals of xeroderm a pigmentosum group E (xeroderma pigmentosum E) have a mild clinical form o f the disease and their cells exhibit a high level of nucleotide excision r epair as measured by unscheduled DNA synthesis, as well as biochemical hete rogeneity. Cell strains from one group of xeroderma pigmentosum E patients have normal damage-specific DNA binding activity (Ddb(+)), whereas others d o not (Ddb(-)). Using a refinement of a previously reported cell fusion com plementation 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 pigmen tosum 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 assign ed to xeroderma pigmentosum group E. With the exception of the Ddb(+) strai n XP89TO, which demonstrated defective nucleotide excision repair, both Ddb (-) and Ddb(+) xeroderma pigmentosum E cells exhibited the same levels of v ariation in unscheduled DNA synthesis that were seen in normal control cell s. 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.