Evidence that Xeroderma Pigmentosum Cells do not Perform the First Step in the Repair of Ultraviolet Damage to their DNA

Xeroderma pigmentosum (XP) is a recessively transmitted disorder of man characterized by increased sensitivity to ultraviolet light. Homozygous, affected individuals, upon exposure to sunlight, sustain severe damage to the skin; this damage is characteristically followed by multiple basal and squamo...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1969-11, Vol.64 (3), p.1035-1041
Main Authors: Setlow, R. B., Regan, James D., German, James, Carrier, W. L.
Format: Article
Language:English
Subjects:
Adult
Biological Sciences: Genetics
Cell lines
Centrifugation, Density Gradient
Consanguinity
Culture Techniques
Dimers
Diploidy
DNA
DNA - biosynthesis
DNA - radiation effects
DNA damage
Fibroblasts
Human genetics
Humans
Male
Molecular Weight
Pedigree
Polymers
Pyrimidine dimers
Pyrimidines
Radiation Genetics
Skin
Skin - cytology
Ultraviolet Rays
Xeroderma Pigmentosum - genetics
Xeroderma Pigmentosum - metabolism
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Summary:Xeroderma pigmentosum (XP) is a recessively transmitted disorder of man characterized by increased sensitivity to ultraviolet light. Homozygous, affected individuals, upon exposure to sunlight, sustain severe damage to the skin; this damage is characteristically followed by multiple basal and squamous cell carcinomas and not uncommonly by other malignant neoplasia. A tissue culture cell line was derived from the skin of a man with XP. Our measurements of ultraviolet-induced pyrimidine dimers in cellular DNA show that normal diploid human skin fibroblasts excise up to 70 per cent of the dimers in 24 hours, but that fibroblasts derived from the individual with XP excise less than 20 per cent in 48 hours. Alkaline gradient sedimentation experiments show that during the 24 hours after irradiation of normal cells a large number of single-strand breaks appear and then disappear. Such changes are not observed in XP cells. XP cells apparently fail to start the excision process because they lack the required function of an ultraviolet-specific endonuclease. These findings, plus earlier ones of Cleaver on the lack of repair replication in XP cells, raise the possibility that unexcised pyrimidine dimers can be implicated in the oncogenicity of ultraviolet radiation.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.64.3.1035