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Life-span reduction in a Drosophila melanogaster strain deficient in excision rapair
Patricia E. Fernández; Enzo R. Muñoz
Departamento de Radiobiología, Comisión Nacional de Energia Atómica, Av. Libertador 8250, 1429 Buenos Aires, Argentina. Send correspondence to E.R.M.
ABSTRACT
The role played by excision repair in the life-span of Drosophila melanogaster was evaluated. The median and maximal life of virgin females and males carrying the X-linked excision repair deficient mei-9a mutant were compared with those of repair proficient flies. Although the distribution of deaths of mei-9a females and males exhibits a higher scattering than that of repair proficient flies, the four life-curves obtained are rectangular. Under the experimental conditions used this fact led us to conclude that in the populations analyzed death is due to senescence. It was also found that the median and maximal life of repair deficient flies are significantly lower than those of the control. The results obtained are attributed to the accumulation of unrepaired or incorrectly repaired DNA damage in mei-9a flies and thus lend support to the view that DNA repair plays an important role in the determination of longevity.
Keywords: Life-span; Drosophila melanogaster; Excision repair.
REFERENCES
Baker, B.S., Boyd, J.B., Carpenter, A.T.A., Green, M.M., Nguyen, T.D., Ripol, P. and Smith, P.D. (1976). Genetic contro1 of meiotic recombination and somatic DNA metabolism in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 73: 4140-4144.
Baker, B.S., Carpenter, A.T.C. and Ripoll, P. (1978). The utilization during mitotic cell division of loci controlling meiotic recombination and disjuntion in Drosophila melanogaster. Genetics 90: 531-578.
Boyd, J.B., Golino, M.D. and Setlow, r.B. (1976). The mei-9a mutant of Drosophila melanogaster increases mutagen sensitivity and decreases excision repair. Genetics 84: 527-544.
Boyd, J.B., Mason, J.M., Yamamoto, A.H., Brodberg, RK., Banga, S.S. and Sakaguchi, K.A. (1987). A genetic and molecular analysis of DNA repair in Drosophila. Cell Sci. Suppl. 6: 39-60.
Cleaver, J.E. (1969). Xeroderma pigmentosum: a human disease in which an initial stage of DNA repair is defective. Proc. Natl. Acad. Sci. USA 63: 428-435.
Cleaver, J.E. (1971). Repair of alkylation damage in ultraviolet-sensitive (xeroderma pigmentosum) human cells. Mutat. Res. 12: 453-462.
Cleaver, J.E. (1984). DNA repair deficiencies and cellular senescence are unrelated in xeroderma pigmentosum cell lines. Mech. Ageing Dev. 27: 189-196.
Drake, J.W. and Baltz, RH. (1976). The biochemistry of mutagenesis. Ann. Rev. Biochem. 45: 11-37.
Dusenbery, RL., McCormick, S.C. and Smith, P.D. (1983). Drosophila mutations at the mei-9aand mus(2)202 loci which block excision of thymine dimers also block induction of unscheduled DNA synthesis by methyl methanesulfonate, ethyl methanesulfonate, N-methyl-N-nitrosourea, UV light and X-rays. Mutat. Res. 112: 215-230.
Epstein, J., Williams, J.R. and Little, J.B. (1974). Rate of DNA repair in progeric and normal human fibroblasts. Biochem. Biophys. Res. Comm. 59: 850-857.
Ferro, W. (1983). Studies on mutagen-sensitive strains of Drosophila melanogaster. II. Detection of qualitative differences between genetic damage induced by X-irradiation of mature spermatozoa in oxygenated and anoxic atmospheres through the use of the repair deficient mutant mei-9a. Mutat. Res. 107: 79-92.
Francis, A.A., Lee, W.H. and Regan, J.D. (1981). The relationship of DNA excision repair of ultraviolet induced lesions to the maximum life-span of mammals. Mech. Ageing Dev. 16: 181-189.
Friedberg, E.C., Ehmann, U.K. and Williams, J.I. (1979). Human diseases associatid with defective DNA repair. In: Advances in Radiation Biology, Vol. 8 (J.T. Lett and H. Adler eds.), Academic Press, New York, pp. 85-174.
Gatti, M. (1979). Genetic contro1 of chromosome breakage and rejoining in Drosophila melanogaster. I. Spontaneous chromosome aberrations in X-linked mutants defective in DNA metabolisms. Proc. Natl. Acad. Sci. USA 76; 1377-1381.
Gensler, H.L. and Bernstein, H. (1981). DNA damage as the primary cause of aging. Q. Rev. Biol. 56: 279-306.
Hall, J.D., Almy, RE. and Scherer, K.L. (1981). DNA repair in cultured human fibroblasts does not decline with donor age. Exp. Cell Res. 139: 351-359.
Hall, K.Y., Hart, R.W., Bernirschke, A.K. and Walford, R.L. (1984). Correlation between ultraviolet-induced DNA repair in primate lymphocytes and fibroblasts and species maximum achievable life-span. Mech. Ageing Dev. 24: 163-173.
Hart, R.W. and Setlow, RB. (1976). DNA repair in late-passage human cells. Mech. Ageing Dev. 5: 67-77.
Hasegawa, N., Hanaoka, F. and Yamada, M.-A. (1984). Increased unscheduled DNA synthesis in aged human diploid fibroblasts. Mech. Ageing Dev. 25: 297-305.
Hasson, E. and Munoz, E.R. (1988). Spontaneous second chromosome recessive lethals in a Drosophila melanogaster repair-deficient mei-9a) mutant. Mutat. Res. 197: 77-83.
Heddle, JA. and Arlen, C.F. (1980). Untransformed xeroderma pigmentosum cells are not hypersensitive to sister-chromatid exchange production by ethyl methanesulfonate-implications for the use of transformed cell lines and for the mechanism by which SCE arise. Mutat. Res. 72: 119-125.
Kato, H., Harada, M., Tsuchiya, K. and Moriwaki, K. (1980). Absence of correlation between DNA repair in ultraviolet irradiated mammalian cells and life-span of the donor species.Jpn.J. Genet. 55: 99-108.
Kleijer, W.J., Bohman, P.H.M., Mulder, M.P. and Bootsma, D. (1970). Repair of X-ray damage in DNA
of cultivated cells from patients having xeroderma pigmentosum. Mutat. Res. 9: 517-523.
Lamb, M.L. (1978). Ageing. In: The Genetics and Biology of Drosophila, Vol. 2c (M. Ashburnerand and T.RF.
Wright eds.), Academic Press, London, pp. 43-104.
Licastro, F. and Walford, R.. (1986). Modulatory effect of nicotinamide on unscheduled DNA synthesis in lymphocytes from young and old mice. Mech. Ageing Deva. 35: 123-131.
Lindsley, D.L. and Grell, E.H. (1968). Genetic variations of Drosophila melanogaster, Carnegie Inst. Wash. Publ., 627. Marquis, J., Binnard, R and Fleming, J.E. (1983). Role of metabolic rate and DNA repair in Drosophila melanogoster aging: Implication for the mitochondria) mutation theory of aging. Exp. Gerontol. 18: 167-171.
Mattern, RM. and Cerutti, PA. (1975). Age-dependent excision repair of damaged thymine from g-irradiated DNA by isolated nuclei from human fibroblasts. Nature 254: 450-452.
Mayer, P.J. and Baker, III, G.T. (1984). Developmental time and adult longevity in two strains of Drosophila melanogaster in a constant low-stress environment. Mech. Ageing Deva. 26: 283-298. Medvedev, ZA. (1984). Age changes of chromatin. A review. Mech. Ageing Dev. 28: 139-154.
Nguyen, T.D. and Boyd, J.B. (1977). The meiotic-9 (mei-9a) mutants of Drosophila melanogaster are deficient in repair replication of DNA. Mol. Gen. Genet. 158: 141-147.
Nguyen, T.D., Boyd, J.B. and Green, M.M. (1979). Sensitivity of Drosophila mutants to chemical carcinogens. Mutat. Res. 63: 67-77.
Ono, T. and Okada, S. (1978). Does the capacity to rejoin radiation induced DNA breaks decline in senescent mice? Int. J. Radiat. Biol. 33: 403-407.
Osgood, CH. J. and Boyd, J.B. (1982). Apurinic endonuclease from Drosophila melanogaster. Reduced enzymatic activity in excision-deficient mutants of the mei-9" and mus(2)201 loci. Mol. Gen. Genet. 186: 235-239.
Pearl, R. (1940). Introduction to Medical Biometry and Statistics, W.B. Saunders Company, Philadelphia, Chap. VIII, pp. 239-254.
Plesko, M.M. and Richardson, A. (1984). Age related changes in unscheduled DNA synthesis by rat hepatocytes. Biochem. Biophys. Res. Comm. 118: 730-735.
Regan, J.D. and Setlow, R.B. (1973). DNA repair in human progeroid cells. Biochem. Biophys. Res. Comm. 59: 858-864.
Setlow, RB., Faulcon, M. and Regan, J.D. (1976). Defective repair of gamma-ray-induced DNA damage in xeroderma pigmentosum cells. Int. J. Radiat. Biol., 29: 125-236.
Smith, P.D., Dusenbery, R.L., Cooper, F.S. and Baumen, C.F. (1981). Examining the mechanism of mutagenesis in DNA repair-deficient strains of Drosophila melanogaster. In: Environmental Mutagens and Carcinogens, (T. Sugimura, S. Kondo and H. Takebe, eds.) University of Tokyo, Alan Liss, New York, pp. 147-152.
Stich, H.F., San, R.H.C. and Kawazoe, Y. (1973). Increased sensitivity of xeroderma pigmentosum cells to some chemical carcinogens and mutagens. Mutat. Res. 17: 127-137.
Targovnik, H.S., Locher, S.E., Hart, T.F. and Hariharan, P.V. (1984). Age-related changes in the excision repair capacity of Tubatrix aceti. Mech. Ageing Dev. 27: 73-81.
Wolff, S., Bodycote, J., Thomas, G.H. and Cleaver, J.E. (1975). Sister chromatid exchange in xeroderma pigmentosum cells that are defective in DNA excision repair or post-replication repair. Genetics 81: 349-355.