Abstract
Human cells contain singular DNA repair pathways to excise critical lesions from DNA (Lindahl, 1982; Teebor and Frenkel, 1983; Friedberg, 1985, Strauss, 1985). Two major excision repair pathways have been identified. In nucleotide excision repair, the DNA adduct is released within an oligonucleotide after sequential action of an undetermined number of enzymes. In contrast, in base excision repair, the DNA adduct is released in the initial enzymatic step of the pathway. This reaction is catalyzed by a DNA glycosylase which cleaves the base-sugar glycosyl bond. Human cells may contain a family of DNA glycosylases each of which may be responsible for the removal of a specific modified base. Thus, the uracil DNA glycoslase removes uracil from DNA. Uracil may arise in DNA by the deamination of cytidine residues (Hayatsu, 1977) or by the incorporation of 5′dUMP during DNA synthesis (Bessman, et al., 1958). The former, by definition, would be a mutagenic event if left unrepaired. Uracil excision results in the formation of an apyrimidinic site in DNA. That site is incised by the apurinic/apyrimidinic acid (AP) endonuclease to form a single strand break. Subsequent catalysis by a DNA polymerase and DNA ligase would be minimal requirements for the completion of base excision repair.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Arenaz, P. and Sirover, M.A., 1983, Isolation and characterization of monoclonal antibodies to the uracil DNA glycosylase from human placenta, Proc. Natl. Acad. Sci., USA, 80:5822.
Bessman, M.J., Lehman, I.R., Adler, J., Zimmerman, S.B., Simns, E.S., and Kornberg, A., 1958, Enzymatic synthesis of DNA. III. The incorporation of purine and pyrimidine analogues into DNA. Proc. Natl. Acad. Sci., USA, 44:633.
Bloom, D., 1966, The syndrome of congenital telangiectatic erythema and stunted growth, J. Pediatrics, 68:103.
Bryant, E.M., Hoehn, H., and Martin, G.M., 1979, Normalization of sister chromatid exchange frequencies in Bloom’s syndrome by euploid cell hybridization. Nature, 279:795.
Chaganti, R.S.K., Schonberg, S. and German, J., 1979, A many fold increase in sister chromatid exchanges in Bloom’s syndrome lymphocytes. Proc. Natl. Acad. Sci., USA, 71:4508.
Chan, J.Y.H., Becker, F.F., German, J., and Ray, J.H., 1987, Altered DNA ligase I activity in Bloom’s syndrome cells. Nature, 325:357.
Dehazya, P. and Sirover, M.A., 1986, Regulation of hypoxanthine DNA glycosylase in normal human and Bloom’s syndrome fibroblasts. Cancer Res., 46:3756.
Doniger, D., DiPaolo, J.A., and Popescu, N.C., 1983, Transformation of Bloom’s Syndrome Fibroblasts by DNA Transfec-tion. Science, 222:1144.
Friedberg, E.C., 1985, DNA Repair, New York, W.H. Freeman and Co.
German, J., 1969, Bloom’s syndrome. I. Genetic and clinical observations in the first 27 patients. Am. J. Hum. Genet., 21:196.
German, J., Bloom, D. and Passarge, E., 1977, Bloom’s syndrome, V. Surveillence for cancer in affected families. Clin. Gen., 12:162.
German, J., Bloom, D. and Passarge, E., 1984, Bloom’s syndrome. XI. Progress report for 1983, Clin. Genet., 254:166.
Gupta, R.S. and Goldstein, S., 1980, Diphtheria toxin resistance in human fibroblast cell strains from normal and cancer-prone individuals, Mutat. Res., 73:331.
Gupta, P.K. and Sirover, M.A., 1980, Sequential stimulation of DNA repair and DNA replication in normal human cells, Mutation Res., 72:273.
Gupta, P.K. and Sirover, M.A., 1981a, Cell cycle regulation of DNA repair in normal and repair deficient human cells, Chem. Biol. Int., 36:19.
Gupta, P.K. and Sirover, M.A., 1981b, Stimulation of the nuclear uracil DNA glycosylase in proliferating human fibroblasts, Cancer Res., 41:3133.
Gupta, P.K. and Sirover, M.A., 1984a, Altered temporal expression of DNA repair in hypermutable Bloom’s syndrome cells, Proc. Natl. Acad. Sci. USA, 81:757.
Gupta, P.K. and Sirover, M.A., 1984b, Regulation of DNA repair in serum stimulated xeroderma pigmentosum cells, J. Cell Biol., 99:1275.
Hayatsu, H., 1977, Co-operative mutagenic actions of bisulfite and nitrogen nucleophiles, J. Mol. Biol., 115:19.
Inoue, T., Hirano, K., Yokoiyama, A., Kata, T., and Kato, H., 1977, DNA repair enzymes in ataxia telangiectasia and Bloom’s syndrome fibroblasts, Biochim. Biophys. Acta, 479:497.
Kim, S., Vollberg, T.M., Ro, J.Y., Kim, M. and Sirover, M.A., 1986, O6-methylguanine methyltransferase increases before S-phase in normal human cells but does not increase in hypermutable Bloom’s syndrome cells, Mutat. Res., 173:141.
Lindahl, T., 1982, DNA Repair Enzymes, Annu. Rev. Biochem., 51:61.
Remsen, J.F., 1980, Repair of damage by N-acetoxy-2-acetyl aminofluorene in Bloom’s syndrome, Mutat. Res., 72:151.
Seal, G. and Sirover, M.A., 1986, Physical association of the human base excision repair enzyme uracil DNA glycosylase with the 70, 000 dalton catalytic subunit of DNA polymerase alpha, Proc. Natl. Acad. Sci. USA, 83:7608.
Seal, G., Arenaz, P. and Sirover, M.A., 1987, Purification and properties of the human placental uracil DNA glycosylase, Biochim. Biophys. Acta., 925:226.
Seal, G., Brech, K., Karp, S.J., Cool, B.J. and Sirover, M.A., 1988, Immunological lesions in human uracil DNA glycosylase: Association with Bloom’s Syndrome, Proc. Natl. Acad. Sci. USA, 85:2339.
Sirover, M.A., 1979, Induction of the DNA repair enzyme uracil DNA glycosylase in stimulated human lymphocytes, Cancer Res., 39:2090.
Sirover, M.A., 1989 “Cell cycle regulation of DNA repair enzymes and pathways” in: Transformation of Human Fibroblasts (G.P. Milo and B.C. Casto, Eds.) CRC Press, Boca Raton, Florida. In Press.
Sirover, M.A. and Gupta, P.K., 1983, “Regulation of DNA Repair in Human Cells” in: Human Carcinogenesis (C.C. Harris and H.N. Autrup, Eds.) Academic Press, New York, 255.
Strauss, B.S., 1985, Cellular Aspects of DNA Repair, Adv. Can. Res., 45:45.
Teebor, G.W. and Frenkel, K., 1983, The Initiation of DNA-Ex-cision Repair, Adv. Cancer Res., 38:23.
Vijayalaxmi, Evans, H.J., Ray, J.H. and German, J., 1983, Bloom’s syndrome: evidence for an increased mutation frequency in vivo, Science, 221:851.
Vollberg, T.M., Cool, B.L. and Sirover, M.A., 1987a, Biosynthesis of the human base excision repair enzyme uracil DNA glycosylase, Cancer Res., 47:123.
Vollberg, T.M., Seal, G. and Sirover, M.A., 1987b, Monoclonal antibodies detect conformational abnormality of uracil DNA glycosylase in Bloom’s syndrome cells, 8:1725.
Warren, S.T., Schultz, R.A., Chang, C.C., Wade, M.H. and Trosko, J.E., 1981, Elevated spontaneous mutation rate in Bloom’s syndrome fibroblasts, Proc. Natl. Acad. Sci. USA, 78:3133.
Willis, A.E. and Lindahl, T., 1987, DNA ligase I deficiency in Bloom’s syndrome, Nature, 325:355.
Willis, A.E., Weksberg, R., Tomlinson, S. and Lindahl, T. 1987. Structural alterations of DNA ligase I in Bloom’s syndrome, Proc. Natl. Acad. Sci. USA, 84:8016.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Plenum Press, New York
About this chapter
Cite this chapter
Sirover, M.A., Seal, G., Vollberg, T.M., Cool, B.L., Brech, K., Karp, S.J. (1989). Detection of Unique Antigenic Lesions in the Uracil DNA Glycosylase from Bloom’s Syndrome. In: Lambert, M.W., Laval, J. (eds) DNA Repair Mechanisms and Their Biological Implications in Mammalian Cells. NATO ASI Series, vol 182. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-1327-4_36
Download citation
DOI: https://doi.org/10.1007/978-1-4684-1327-4_36
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-1329-8
Online ISBN: 978-1-4684-1327-4
eBook Packages: Springer Book Archive