Abstract
The three miscoding alkylated pyrimidines O2-methylcytosine, O2-methylthymine and O4-methylthymine are specifically recognized by Escherichia coli DNA repair enzymes. The activities are induced as part of the adaptive response to alkylating agents. O2-Methylcytosine and O2-methylthymine are removed by a DNA glycosylase, the alkA+ gene product, which also acts on N3-methylated purines. O4-Methylthymine is repaired by a methyltransferase, previously known to correct O6-methylguanine by transfer of the methyl group to one of its own cysteine residues. It is proposed that certain common structural features of the various methylated bases allow each of the two inducible repair enzymes to recognize and remove several different kinds of lesions from alkylated DNA.
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- Abbott P. J., Saffhill R. DNA synthesis with methylated poly(dC-dG) templates. Evidence for a competitive nature to miscoding by O(6)-methylguanine. Biochim Biophys Acta. 1979 Mar 28;562(1):51–61. doi: 10.1016/0005-2787(79)90125-4. [DOI] [PubMed] [Google Scholar]
- Bartsch H., Terracini B., Malaveille C., Tomatis L., Wahrendorf J., Brun G., Dodet B. Quantitative comparison of carcinogenicity, mutagenicity and electrophilicity of 10 direct-acting alkylating agents and of the initial O6:7-alkylguanine ratio in DNA with carcinogenic potency in rodents. Mutat Res. 1983 Aug;110(2):181–219. doi: 10.1016/0027-5107(83)90140-9. [DOI] [PubMed] [Google Scholar]
- Beranek D. T., Heflich R. H., Kodell R. L., Morris S. M., Casciano D. A. Correlation between specific DNA-methylation products and mutation induction at the HGPRT locus in Chinese hamster ovary cells. Mutat Res. 1983 Jun-Jul;110(1):171–180. doi: 10.1016/0027-5107(83)90026-x. [DOI] [PubMed] [Google Scholar]
- Beranek D. T., Weis C. C., Swenson D. H. A comprehensive quantitative analysis of methylated and ethylated DNA using high pressure liquid chromatography. Carcinogenesis. 1980 Jul;1(7):595–606. doi: 10.1093/carcin/1.7.595. [DOI] [PubMed] [Google Scholar]
- Bodell W. J., Singer B., Thomas G. H., Cleaver J. E. Evidence for removal at different rates of O-ethyl pyrimidines and ethylphosphotriesters in two human fibroblast cell lines. Nucleic Acids Res. 1979 Jun 25;6(8):2819–2829. doi: 10.1093/nar/6.8.2819. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cairns J., Robins P., Sedgwick B., Talmud P. The inducible repair of alkylated DNA. Prog Nucleic Acid Res Mol Biol. 1981;26:237–244. doi: 10.1016/s0079-6603(08)60408-0. [DOI] [PubMed] [Google Scholar]
- Conrad S. E., Campbell J. L. Characterization of an improved in vitro DNA replication system for Escherichia coli plasmids. Nucleic Acids Res. 1979 Jul 25;6(10):3289–3304. doi: 10.1093/nar/6.10.3289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Demple B., Jacobsson A., Olsson M., Robins P., Lindahl T. Repair of alkylated DNA in Escherichia coli. Physical properties of O6-methylguanine-DNA methyltransferase. J Biol Chem. 1982 Nov 25;257(22):13776–13780. [PubMed] [Google Scholar]
- Evensen G., Seeberg E. Adaptation to alkylation resistance involves the induction of a DNA glycosylase. Nature. 1982 Apr 22;296(5859):773–775. doi: 10.1038/296773a0. [DOI] [PubMed] [Google Scholar]
- Hall J. A., Saffhill R. The incorporation of O6-methyldeoxyguanosine and O4-methyldeoxythymidine monophosphates into DNA by DNA polymerases I and alpha. Nucleic Acids Res. 1983 Jun 25;11(12):4185–4193. doi: 10.1093/nar/11.12.4185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jensen D. E. Reaction of DNA with alkylating agents. Differential alkylation of poly[dA-dT[ by methylnitrosourea and ethylnitrosourea. Biochemistry. 1978 Nov 28;17(24):5108–5113. doi: 10.1021/bi00617a006. [DOI] [PubMed] [Google Scholar]
- Jensen D. E., Reed D. J. Reaction of DNA with alkylating agents. Quantitation of alkylation by ethylnitrosourea of oxygen and nitrogen sites on poly[dA-dT] including phosphotriester formation. Biochemistry. 1978 Nov 28;17(24):5098–5107. doi: 10.1021/bi00617a005. [DOI] [PubMed] [Google Scholar]
- Karran P., Hjelmgren T., Lindahl T. Induction of a DNA glycosylase for N-methylated purines is part of the adaptive response to alkylating agents. Nature. 1982 Apr 22;296(5859):770–773. doi: 10.1038/296770a0. [DOI] [PubMed] [Google Scholar]
- Karran P., Lindahl T. Enzymatic excision of free hypoxanthine from polydeoxynucleotides and DNA containing deoxyinosine monophosphate residues. J Biol Chem. 1978 Sep 10;253(17):5877–5879. [PubMed] [Google Scholar]
- Karran P., Lindahl T., Griffin B. Adaptive response to alkylating agents involves alteration in situ of O6-methylguanine residues in DNA. Nature. 1979 Jul 5;280(5717):76–77. doi: 10.1038/280076a0. [DOI] [PubMed] [Google Scholar]
- Lawley P. D., Orr D. J., Shah S. A., Farmer P. B., Jarman M. Reaction products from N-methyl-N-nitrosourea and deoxyribonucleic acid containing thymidine residues. Synthesis and identification of a new methylation product, O4-methylthymidine. Biochem J. 1973 Sep;135(1):193–201. doi: 10.1042/bj1350193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lawley P. D., Warren W. Removal of minor methylation products 7-methyladenine and 3-methylguanine from DNA of Escherichia coli treated with dimethyl sulphate. Chem Biol Interact. 1976 Feb;12(2):211–220. doi: 10.1016/0009-2797(76)90100-9. [DOI] [PubMed] [Google Scholar]
- Lindahl T. DNA repair enzymes. Annu Rev Biochem. 1982;51:61–87. doi: 10.1146/annurev.bi.51.070182.000425. [DOI] [PubMed] [Google Scholar]
- Lindahl T., Demple B., Robins P. Suicide inactivation of the E. coli O6-methylguanine-DNA methyltransferase. EMBO J. 1982;1(11):1359–1363. doi: 10.1002/j.1460-2075.1982.tb01323.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindahl T., Ljungquist S., Siegert W., Nyberg B., Sperens B. DNA N-glycosidases: properties of uracil-DNA glycosidase from Escherichia coli. J Biol Chem. 1977 May 25;252(10):3286–3294. [PubMed] [Google Scholar]
- Olsson M., Lindahl T. Repair of alkylated DNA in Escherichia coli. Methyl group transfer from O6-methylguanine to a protein cysteine residue. J Biol Chem. 1980 Nov 25;255(22):10569–10571. [PubMed] [Google Scholar]
- Robins P., Harris A. L., Goldsmith I., Lindahl T. Cross-linking of DNA induced by chloroethylnitrosourea is presented by O6-methylguanine-DNA methyltransferase. Nucleic Acids Res. 1983 Nov 25;11(22):7743–7758. doi: 10.1093/nar/11.22.7743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Samson L., Cairns J. A new pathway for DNA repair in Escherichia coli. Nature. 1977 May 19;267(5608):281–283. doi: 10.1038/267281a0. [DOI] [PubMed] [Google Scholar]
- Sancar A., Rupp W. D. A novel repair enzyme: UVRABC excision nuclease of Escherichia coli cuts a DNA strand on both sides of the damaged region. Cell. 1983 May;33(1):249–260. doi: 10.1016/0092-8674(83)90354-9. [DOI] [PubMed] [Google Scholar]
- Sedgwick B., Robins P. Isolation of mutants of Escherichia coli with increased resistance to alkylating agents: mutants deficient in thiols and mutants constitutive for the adaptive response. Mol Gen Genet. 1980;180(1):85–90. doi: 10.1007/BF00267355. [DOI] [PubMed] [Google Scholar]
- Singer B. All oxygens in nucleic acids react with carcinogenic ethylating agents. Nature. 1976 Nov 25;264(5584):333–339. doi: 10.1038/264333a0. [DOI] [PubMed] [Google Scholar]
- Singer B., Kröger M., Carrano M. O2- and O4-alkyl pyrimidine nucleosides: stability of the glycosyl bond and of the alkyl group as a function of pH. Biochemistry. 1978 Apr 4;17(7):1246–1250. doi: 10.1021/bi00600a018. [DOI] [PubMed] [Google Scholar]
- Singer B., Spengler S., Bodell W. J. Tissue-dependent enzyme-mediated repair or removal of O-ethyl pyrimidines and ethyl purines in carcinogen-treated rats. Carcinogenesis. 1981;2(10):1069–1073. doi: 10.1093/carcin/2.10.1069. [DOI] [PubMed] [Google Scholar]
- Singer B., Sági J., Kuśmierek J. T. Escherichia coli polymerase I can use O2-methyldeoxythymidine or O4-methyldeoxythymidine in place of deoxythymidine in primed poly(dA-dT).poly(dA-dT) synthesis. Proc Natl Acad Sci U S A. 1983 Aug;80(16):4884–4888. doi: 10.1073/pnas.80.16.4884. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas L., Yang C. H., Goldthwait D. A. Two DNA glycosylases in Escherichia coli which release primarily 3-methyladenine. Biochemistry. 1982 Mar 16;21(6):1162–1169. doi: 10.1021/bi00535a009. [DOI] [PubMed] [Google Scholar]
- Warner H. R., Rockstroh P. A. Incorporation and excision of 5-fluorouracil from deoxyribonucleic acid in Escherichia coli. J Bacteriol. 1980 Feb;141(2):680–686. doi: 10.1128/jb.141.2.680-686.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]