Abstract
Treatment of cells with alkylating agents results in DNA modification. The reaction products are alkylpurines, phosphotriesters and some minor products such as alkylpyrimidines. Some of them are repaired by alkyl DNA transferase while others are repaired by DNA glycosylases which generate as products the free alkylated base and an apurinic site (AP-site). This is a secondary lesion which is harmful to the cell and is actively repaired. Alkylation of the N7 of guanine labilizes i) the glycosidic bond yielding an AP-site and ii) the imidazole ring leading to the corresponding formamidopyrimidine, another secondary lesion. We review the biological implications of AP-sites and the formamidopyrimidine lesion which may form following alkylation of DNA.
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
P.D. Lawley, Methylation of DNA by carcinogens: Some applications of chemical analytical methods. In ‘Screening test in chemical carcinogenesis“, IARC, Scientific publications, n° 12:181–208 (1976).
B. Singer and D. Grunberger, in: Molecular Biology of Mutagens and Carcinogens. Plenum Press. NY 143–199 (1983).
S. Boiteux, O, Huisman and J. Laval, III-methyladenine residues in DNA induce the SOS function sfiA in Escherichia coli, EMBO J. 3: 2569–2573 (1984).
P. Karran, T. Lindahl, G. Ofsteng, B. Evensen and E. Seeberg, Escherichia coli mutants deficient in 3-methyladenine-DNA glycosylase, J. Mol. Biol. 140: 101–127 (1980).
A. Loveless, Possible relevance of O6-alkylation of deoxyguanosine to the mutagenicity and carcinogenicity of nitrosamines and nitrosamides, Nature 223: 206–207 (1969).
Laaval and F. Laval, Enzymology of DNA repair in: Molecular and Cellular aspects of carcinogen screening tests, Ì ARC Scientific publications, 27:55–73 (1980).
I. Teo, B. Sedgwick, M.W. Kilpatrick, T.V. McCarthy and T. Lindahl, The intracellular signal for induction of resistance to alkylating agents in E. coli, Cell 45: 315–324 (1986).
J.A. Haines, C.B. Ree and L. Todd, Methylation of guanosine and related compounds with diazomethane, J. Chem. Soc., 5281 (1962).
N.D. Clarke, M. Kvaal and E. Seeberg, Cloning of Escherichia coli genes encoding 3-methyladenine DNA glycosylase I and II, Molec. Gen. Genet. 197: 368–372 (1984).
S. Riazuddin and T. Lindahl, Properties of 3-methyladenine-DNA glycosylase from Escherichia coli, Biochemistry 17: 2110–2118 (1978).
S. Bjelland and E. Seeberg, Purification and characterization of 3methyladenine DNA glycosylase I from Escherichia coli, Nucl. Acid. Res. 7: 2787–2801 (1987).
L. Thomas, C.H. Yang and D.A. Goldthwait, Two DNA glycosylases in Escherichia coli which release primarily 3-methyladenine, Biochemistry 21: 1162–1169 (1982).
J. Pierre and J. Laval, Cloning of Micrococcus luteus 3-methyladenineDNA glycosylase in Escherichia coli, Gene 43: 139–146 (1986).
R. Male, D. Helland and K. Kleppe, FiRTication and characterization of 3-methyladenine-DNA glycosylase from calf thymus, J. Biol. Chem. 260: 1623–1629 (1985).
P.E. Gallagher and T.P. Brent, Further purification and characterization of human 3-methyladenine-DNA glycosylase. Evidence for broad specificity, Biochem. Biophys. Acta 782: 394–401 (1984).
P.E. Gallagher and T.P. Brent, Partial purification of a human 3methyladenine-DNA glycosylase from human placenta, Biochemistry 21: 6404–6409 (1982).
Y. Nakabeppu, H. Kondo and M. Sekiguchi, Cloning and characterization of the alkA gene of Escherichia coli that encodes 3-methyladenine DNA glycosylase II, J. Biol. Chem. 259: 13723–13729.
R. Shapiro, Damage to DNA caused by hydrolysis, in: Chromosome Damage and Repair, E. Seeberg and K. Kleppe, ed., Plenum Press New York and London, pp: 3–18 (1981).
S.G. Rogers and B. Weiss, Exonuclease III of Escherichia coli K-12, and AP Endonuclease, Methods in Enzymology 65: 201–211 (1980).
R.P. Cunningham, S.M. Saporito, S.G. Spitzer and B. Weiss, Endonuclease IV (nfo) mutant of Escherichia coli, J. Bact. 168: 1120–1127 (1986).
R.P. Cunningham and B. Weiss, Endonuclease III (nth) mutants of Escherichia coli, Proc. Natl. Acad. Sci. USA 82: 474–477 (1985).
V. Bailly and W.G. Verly, Escherichia coli endonuclease III is not an endonuclease but a 13-elimination catalyst, Biochem. J. 242: 565–572.
P.R. Armei and S.S. Wallace, Apurinic endonucleases from Saccharomyces cerevisiae, Nucl. Acids Res. 5: 3347–3356 (1978).
J. Svachulova, J. Satava and J. Veliminsky, A Barley Endonuclease specific for apurinic DNA, Eur. J. Biochem. 87: 215–220 (1978).
L. Thibodeau and W.G. Verly, Purification and properties of a plant Endonuclease specific for apurinic sites, J. Biol. Chem. 252: 3304–3309 (1977).
C.M. Kane and S. Linn, Purification and characterization of an Apurinic/Apyrimidinic Endonuclease from HeLa cells, J. Biol. Chem. 256: 3405–3415 (1981).
P.D. Lawley and D.J. Orr, Specific excision of methylation products from DNA of Escherichia coli treated with N-methyl-N’-nitro-N-nitrosoguanidine, Chem. Biol. Interact. 2: 154–157 (1970).
S. Boiteux, J. Belleney, B.P. Roques and J. Laval, Two rotameric forms of open ring 7-methylguanine are present in alkylated polynucleotides, Nucl. Acids. Res. 12: 5429–5439.
S. Boiteux and J. Laval, Imidazole open ring 7-methylguanine: An inhibitor of DNA synthesis, Biochem. Biophys. Res. Commun. 110: 552–558 (1985).
C.J. Chetsanga and T. Lindahl, Release of 7-methylguanine residues whose imidazole ring have been opened from damaged DNA, by a DNAglycosylase from E. coli, Nucl. Acids Res. 6: 3673–3683 (1979).
S. Boiteux, T.R. O’Connor and J. Laval, Formamidopyrimidine-DNA glycosylase of Escherichia coli: Cloning and sequencing of the fpg structural gene and overproduction of the protein, EMBO J. 6: 3177–3183 (1987).
B. Demple, A. Johnson and D. Fung, Exonuclease III and endonuclease IV remove 3’ blocks from DNA synthesis primers in H202-damaged Escherichia coli, Proc. Natl. Acad. Sci. USA. 13: 7731–7735 (1986).
S. Boiteux and J. Laval, Coding properties of Poly(deoxycytidilic acid) templates containing uracil or apyrimidinic sites: In vitro modulation of mutagenesis by deoxyribonucleic acid repair enzymes, Biochemistry 21: 6746–6751 (1982).
L.A. Loeb, Apurinic sites as mutagenic intermediates, Cell 40: 483–484 (1985).
R.M. Shaaper, B.W. Glickman, L.A. Loeb, Role of depurination in muta-genesis by chemical carcinogens, Cancer Res. 42: 3480–3485 (1982).
A. Gentil, A. Margot and A. Sarasin, Apurinic sites cause mutations in simian virus 40, Mut. Res. 129: 141–147 (1984).
N. Müller and G. Eisenbrand, The influence of N7-substituents on the stability of N7-alkylated guanosines, Chem. Biol. Interact. 53: 173–181 (1985).
T.R. Irvin and G.N. Wogan, Quantitation of aflatoxin B, adduction within the ribosomal RNA gene sequences of rat liver DNA, Proc. Natl. Acad. Sci. USA 81: 664–668 (1984).
E. Kriek and J.G. Westra, Structural identification of the pyrimidine derivatives formed from N-(deoxyguanosin-8-y1)-2-aminofluorene in aqueous solution at alkaline pH, Carcinogenesis 1: 459–468 (1980).
C.J. Chetsanga, G. Polidori and M. Mainwaring, Analysis and excision of phosphoramide mustard-deoxyguanosine adducts in DNA, Cancer Res. 42: 2616–2621 (1982).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Springer Science+Business Media New York
About this chapter
Cite this chapter
Laval, J., O’Connor, T.R., Boiteux, S. (1989). Repair of Secondary Lesions Arising in DNA after Treatment with Alkylating Agents. In: Castellani, A. (eds) DNA Damage and Repair. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-5016-4_14
Download citation
DOI: https://doi.org/10.1007/978-1-4757-5016-4_14
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-5018-8
Online ISBN: 978-1-4757-5016-4
eBook Packages: Springer Book Archive