The Mer Phenotype: Human Tumor Cell Strains Defective in Repair of Alkylation Damage
The integrity of DNA is vitally important to cellular function and a wide variety of organisms possess repair mechanisms to preserve DNA structure and its faithful replication. Much of our understanding of human DNA repair comes from the study of xeroderma pigmentosum (XP). Patients with this disease show sun sensitivity and a high incidence of skin cancer among their symptoms [for review see 1,2]. XP is inherited in a Mendelian fashion and cells from many tissues of XP patients show hypersensitivity to UV, suggesting that a germ line mutation is responsible for the disease. In addition to cellular hypersensitivity, XP cells are deficient in support of growth of UV-irradiated SV40, herpes simplex virus and and adenovirus3,4,5. XP cells grown in culture fail to remove UV-induced pyrimidine dimers from their DNA while normal cells do6. UV-irradiated XP cells have been permeabilized and supplied with exogenous endonucleases which incise UV-irradiated DNA, whereupon dimers were excised and cellular hypersensitivity was reduced7’8. These data suggest that in XP a germ line mutation results in inactivation of excision repair of pyrimdine dimers throughout the body and the persistence of high levels of pyrimidine dimers in epidermal DNA leads to oncogenic transformation.
KeywordsGerm Line Mutation Xeroderma Pigmentosum Pyrimidine Dimer Alkylation Damage MNNG Treatment
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- 1.Kraemer, K. (1980) Clinical Derm. 4: 1–33.Google Scholar
- 4.Lytle, C.D., S.A. Aaronson and E. Harvey (1972) Intl. J. Rad. Biol. 22: 159–165.Google Scholar
- 9.Day, R.S. III, C.H.J. Ziolkowski, D.A. Scudiero, S.A. Meyer and M.R. Mattern (1980) in “Genetic and Environmental Factors in Experimental and Human Cancer” H.V. Gelboin et al. eds. Japan Sci. Soc. Press, Tokyo, pp 247–257.Google Scholar
- 11.Day, R.S. III and C.H.J. Ziolkowski (1981) Carcinogenesis 2:213218.Google Scholar
- 19.Setlow, R.B. and J.D. Regan (1981) in “Techniques in DNA Repair-A Handbook” E.C. Friedberg and P.C. Hanawalt eds., Marcel Dekker, Inc. N.Y. pp 307–318.Google Scholar