thesis
DNA repair in human xeroderma pigmentosum and Chinese hamster cells
- Publication date
- 1 January 1980
- Publisher
- 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.