An important feature of living cells is their capacity to maintain the integrity of their hereditary material, the DNA. DNA can be damaged by a variety of physical and chemical agents, among which ultraviolet radiation (UV), ion1z1ng radiation and chemical carcinogens as 4-nitroquinoline-1-oxide (4NQO). Most organisms, including man, are able to repair damaged DNA. The DNA repair processes play a very important role, which is demonstrated by the inherited skin disease xeroderma pigmentosum (XP). This disease is manifested primarily by cellular atrophy, pigmentation abnormalities and malignancies in the sun-exposed areas of the skin. Some of the affected individuals also have neurological complications. Cells derived from most XP patients are abnormally sensitive to UV, which is ascribed to the fact that these cells show a reduced unscheduled DNA synthesis after UV-irradiation and appear to be deficient in the excision of pyrimidine dimers from their DNA. Cultured cells from another group of XP patients show a normal excision repair, but are thought to have a defect in a process associated with the circumvention of lesions present in the DNA during replication (postreplication repair). These are designated as XP variants. The clinical heterogeneity observed in this disease suggested the possibility of differences in the nature of the genetic defects in different patients (genetic heterogeneity). Genetic heterogeneity can be studied with the aid of complementation analysis, by fusion of cells derived from different patients. In several combinations the presence of the genomes of two patients in a hybrid binuclear cell resulted in a normal level of DNA repair,/ suggesting that these patients have a mutation at different sites in the genome. Excision repair-defective XP cell strains have now been classified in 7 complementation groups.

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D. Bootsma (Dirk)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

Zelle, B. (1980, January 30). DNA repair in human xeroderma pigmentosum and Chinese hamster cells. Retrieved from