Abstract
Alkylating agents react with various molecules, specially with nucleic acids. The interaction of these agents with DNA has been extensively studied, and the relative amounts of the various adducts formed either in vitro or in vivo have been measured ( 1 ). Some adducts, such as 3-methyl adenine ( 3-MeAd ) are lethal lesions, some such as O6 -methylguanine ( O6 -MeGua ) or O4 -methylthymine ( O4 -MeThy ) are mutagenic lesions ( reviewed in 2 ). In bacteria, the repair of alkylated residues in DNA occurs by two different processes. Some alkylated bases ( e.g. 3-MeAd ) are removed by a specific glycosylase which forms an apurinic or an apyrimidinic site ( AP site ), which is in turn repaired by the sequential actions of an AP-endonuclease, a DNA polymerase and a DNA ligase ( 3 ). Other alkylated residues (e.g. O6 -MeGua, O4 -MeThy ) are repaired by a transferase which transfers the methyl group from the alkylated base to one of its own cystein residues ( 4–5 ).
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
B. SINGER and D. GRUNBERGER, “Molecular Biology of Mutagens and Carcinogens”, Plenum Press, New York,(1983).
R. SAFFHILL, G.P. MARGISON, and P.J. O’CONNOR, Mechanisms of carcinogenesis induced by alkylating agents, Biochim. Biophys. Acta 823: 111 (1985).
J. LAVAL, Two enzymes are required for strand incision in repair of alkylated DNA, Nature (London) 269: 829 (1977)
B. DEMPLE, A. JACOBSON, M. OLSSON, P. ROBINS and T. INDAHL, Repair of alkylated DNA in E.coli: physical properties of 0 -methylguanineDNA-methyltransferase, J. Biol. Chem. 257: 13776 (1982)
Z. AHMMED and J. LAVAL, Enzymatic rpair of 0 alkylated thymidine residues in DNA: involvement of a 0 -methylthymine-DNA methyltransferase and a 0 -methylthymine DNA glycosylase, Biochim. Biophys. Res. Comm. 120: 1 (1984).
G.C. WALKER, Mutagenesis and inducible responses to deoxyribonucleic acid damage in Escherichia coli, Microbiological Reviews 48: 60 (1984)
P. KARRAN, T. HJELMGREEN and T. LINDAHL, Induction of a glycosylase for N-methylated purines is part of the adaptive response to alkylating agents, Nature (London) 296: 770 (1982)
G. EVENSON and E. SEEBERG, Adaptation to alkylation resistance involves the induction of a DNA glycosylase, Nature (London) 296: 773 (1982)
A.E. PEGG “Reviews in Biochemical Toxicology”, Hodgson,E. Bend,J.R. and Philpot,R.M. eds, Elsevier Biochimical Press, Amsterdam,(1983).
I. TEO, B. SEDGWICK, M.W. KILPATRICK, T.V. McCARTHY and T. LINDAHL, T.e intracellular signal for induction of resistance to alkylating agents in E.coli, Cell 45: 315 (1986)
R. MALE, D.E. HELLAND and K. KLEPPE, Purification and characterization of a 3-methyladenine-DNA glycosylase from calf thymus, J. Biol. Chem. 260: 1623 (1985).
J.F. HORA, A. EASTMAN and E. BRESNICK, 06-methylguanine methyltransferase in rat liver, Biochemistry 22: 3759 (1983).
L.SAMSON and J.L.SCHWARTZ, Evidence for an adaptive DNA repair pathway in CHO cells and human skin fibroblasts cell lines, Nature (London) 287: 861 (1980).
B. KAINA, Enhanced survival and reduced mutation and aberration frequencies induced in V 79 Chinese hamster cells pre-exposed to low levels of methylating agents, Mut. Res. 93: 195 (1982).
F. LAVAL and J. LAVAL, Adaptive response in manmalian cells: crossreactivity of different pretreatments on cytotoxicity as contrasted to mutagenicity, Proc. Natl. Acad. Sci. USA, 81: 1062 (1984).
F. LAVAL, Repair of mehtylated bases in mammalian cells during adaptive response to alkylating agents, Biochimie, 67: 361 (1985).
G.P. MARGISON, Chronic or acute administration of various dialkylnitrosamines enhances the removal of 0 -methylguanine from rat liver DNA in vitro, Chem.biol. Inter. 38: 189 (1982).
G.P. MARGISON, K. BUTLER and B. HOEY, 06-methylguanine-methyltransferase activity is increased in rat tissues by ionising radiations, Carcinogenesis, 6: 1699 (1985).
G. FROSINA and F. LAVAL, The 06-methylguanine-DNA-methyltransferase activity of rat hepatoma cells is increased after a single exposure to alkylating agents, Carcinogenesis, 8: 91 (1987).
P. LEFEBVRE and F. LAVAL, Enhancement of 06-methylguanine-DNA-methyltransferase activity induced by various treatments in mammalian cells Cancer Res. 46: 5791 (1986).
A. LOVELESS, POssible relevance of 06 alkylation of deoxyguanosine to the mutagenicity and carcinogenicity of nitrosamines and nitrosamides, Nature (London) 223: 206 (1969).
S. SUKUMAR, V. NOTARIO, D. MARTIN-ZANCA and M. BARBACID, Induction of mammary carcinomas in rats by nitroso-methylurea involves malignant activation of H-ras-1 locus by single point mutation, Nature (London) 306: 658 (1983).
G. FROSINA and A. ABBONDANDOLO, The current evidence for an adaptive response to alkylating agents in mammalian cells, with special reference to experiments with in vitro cell cultures, Mut. Res. 154: 85 (1985).
J. HUET and F. LAVAL, DNA repair in relation to biological monitoring of exposure to mutagens and acrcinogens, IARC Sci. Pub. 59: 371 (1984)
M.J. SCHLESINGER, M. ASHBURNER and A. TISSIERES, Heat shock: from bacteria to man, Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory (1982).
G.R. STARK and G.M. WAHL, Gene amplifacation, Annu. Rev. Biochem. 53: 447 (1984).
A. BURKLE, T. MEYER, H. HILTZ and H. ZUR HAUSEN, Enhancement of MNNGinduced DNA amplification in a Simian Virus 40-transformed chinese hamster cell line by 3-aminobenzamide, Cancer Res. 47: 3632 (1987).
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
Lefebvre, P., Laval, F. (1989). Inducible Repair of Alkylated Bases in Mammalian Cells. In: Castellani, A. (eds) DNA Damage and Repair. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-5016-4_15
Download citation
DOI: https://doi.org/10.1007/978-1-4757-5016-4_15
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-5018-8
Online ISBN: 978-1-4757-5016-4
eBook Packages: Springer Book Archive