Xeroderma pigmentosum variants have decreased repair of ultraviolet-damaged DNA.

Abstract

XERODERMA pigmentosum (XP) is an inherited human disease characterised by the development of pigmentation abnormalities and numerous malignancies on sun-exposed areas1. Fibroblasts from typical patients with XP are defective in the repair of ultraviolet-produced damage of their DNA: These cells show (with respect to normal fibroblasts) decreased amounts of ultraviolet-induced unscheduled DNA synthesis1–3, less ultraviolet-induced uptake of bromodeoxyuridine into parental DNA (refs 2 and 4), and greater sensitivity to ultraviolet irradiation in terms of colony forming ability5–7. The relationship of the DNA repair defect(s) to the clinical manifestations of XP, however, has been obscured by the finding of a group of patients, designated XP ‘variants’8, who have the clinical manifestations of the disease1,8, but whose cells lack the repair defects (Table 1). Using a sensitive host-cell reactivation technique, I have found that fibroblasts from patients belonging to all five known variant kindreds have defects in the repair of DNA damaged by ultraviolet irradiation.