Summary
The methylating agent N-methyl-N′-nitro-N-nitrosoguanidine preferentially induces G:C to A:T transitions at DNA base pairs with the G in one particular strand of the cI gene in a lambda prophage, in this case the non-transcribed straind, in Escherichia coli cells in which the adaptive response is induced. The same preference is found for the cI gene inserted in the genome in the inverse orientation, so the differential effect is not caused by the direction of motion of the DNA replicating fork.
Similar content being viewed by others
References
Cerda-Olmedo E, Hanawalt PC, Guerola N (1968) Mutagenesis of the replication point by nitrosoguanidine: map and pattern of replication of the Escherichia coli chromosome. J Mol Biol 33:705–719
Coulondre C, Miller JH (1977) Genetic studies of the lac repressor IV. J Mol Biol 117:577–606
Daniels DL, Schroeder JL, Szybalski W, Sanger F, Blattner FR, (1983) Complete annotated lambda sequence. In: Hendrix RW, Roberts JW, Stahl FW, Weisberg RA (eds) Lambda II, Appendix II. Cold Spring Harbor Laboratory, New York, pp 519–676
Demple B, Sedgwick B, Robins P, Totty N, Waterfield MD, Lindahl T (1985) Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis. Proc Natl Acad Sci USA 82:2688–2692
Foster L, Eisenstadt E (1985) Induction of transversion mutations in Escherichia coli by N-methyl-N′-nitro-N-nitrosoguanidine is SOS dependent. J Bacteriol 163:213–220
Hall JA, Saffhill R (1983) The incorporation of O6-methyldeoxyguanosine and O4-methyldeoxythymidine monophosphates into DNA by DNA polymerases I and alpha. Nucleic Acids Res 11:4185–4193
Harris AL, Karran P, Lindahl T (1983) O6-Methylguanine-DNA methyltransferase of human lymphoid cells: Structural and kinetic properties and absence in repair-deficient cells. Cancer Res 43:3247–3252
Hecht MH, Sauer RT (1985) Phage lambda repressor revertants: Amino acid substitutions that restore activity to mutant proteins. J Mol Biol 186:53–63
Hora JF, Eastman A, Bresnick E (1983) O6-Methylguanine methyltransferase in rat liver. Biochemistry 22:3759–3763
Hutchinson F, Wood RD (1987) The determination of sequence changes induced by mutagenesis of the CI gene of lambda phage. In: Friedberg EC, Hanawalt PC (eds) DNA repair: A laboratory manual of research procedures, vol III. Marcel Dekker, New York (in press)
Karran P, Marinus MG (1982) Mismatch correction at O6-methylguanine residues in E. coli DNA. Nature 296:868–9
Karran P, Hjelmgren T, Lindahl T (1982) Induction of a DNA glycosylase for N-methylated purines is part of the adaptive response to alkylating agents. Nature 296:770–773
Lindahl T, Demple B, Robins P (1982) Suicide inactivation of the E. coli O6-methyl-guanine-DNA methyltransferase. EMBO J 1:1359–1363
Loechler EL, Green CL, Essigmann JM (1984) In vitro mutagenesis by O6-methylguanine built into a unique site in a viral gene. Proc Natl Acad Sci USA 81:6271–75
Lu A-L, Welsh K, Su S-S, Modrich P (1984) Repair of DNA base-pair mismatches in vitro. Cold Spring Harbor Symp Quant Biol 49:589–596
Lucchesi P, Carraway M, Marinus MG (1986) Analysis of forward mutations induced by N-methyl-N′-nitro-N-nitrosoguanidine in the bacteriophage P22 mnt repressor gene. J Bacteriol 166:34–37
McCarthy TV, Karran P, Lindahl T (1984) Inducible repair of O-alkylated DNA pyrimidines in Escherichia coli. EMBO J 3:545–550
Messing J (1983) New M13 vectors for cloning. Methods Enzymol 101:20–78
Olsson M, Lindahl T (1980) Repair of alkylated DNA in Escherichia coli: methyl group transfer from O6-methylguanine to a protein cysteine residue. J Biol Chem 255:10569–10571
Pukkila PJ, Peterson J, Herman G, Modrich P, Meselson M (1983) Effects of high levels of DNA adenine methylation on methyldirected mismatch repair in Escherichia coli. Genetics 104:571–582
Robins P, Cairns J (1979) Quantitation of the adaptive response of alkylating agents. Nature 280:74–76
Samson L, Cairns J (1977) A new pathway for DNA repair in E. coli. Nature 267:281–282
Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467
Sauer RT (1978) DNA sequence of the bacteriophage lambda cI gene. Nature 276:301–302
Schendel PF, Defais M, Jeggo P, Samson L, Cairns J (1978) Path-ways to mutagenesis and repair in Escherichia coli exposed to low levels of simple alkylating agents. J Bacteriol 135:466–75
Singer B, Sagi J, Kusmierek JT (1983) Escherichia coli polymerase I can use O2-methyldeoxythymidine or O4-methyldeoxythymidine in place of deoxythymidine in primed poly (dA-dT) synthesis. Proc Natl Acad Sci USA 80:4884–8
Sklar R, Strauss B (1980) The role of the uvrE gene product and of inducible O6-methylguanine removal in the induction of mutations by N-methyl-N′-nitro-N-nitrosoguanidine in Escherichia coli. J Mol Biol 143:343–62
Skopek TR, Hutchinson F (1982) DNA base sequence changes induced by bromouracil mutagenesis of lambda phage. J Mol Biol 159:19–33
Volkert MR, Nguyen DC (1984) Induction of specific Escherichia coli genes by sublethal treatments with alkylating agents. Proc Natl Acad Sci USA 81:4110–4114
Volkert MR, Nguyen DC, Beard KC (1986) Escherichia coli gene induction by alkylation treatment. Genetics 112:11–26
Wood RD (1985) Pyrimidine dimers are not the principal premutagenic lesions induced in lambda phage DNA by ultraviolet light. J Mol Biol 184:577–585
Author information
Authors and Affiliations
Additional information
Communicated by N.D.F. Grindley
Rights and permissions
About this article
Cite this article
Reed, J., Hutchinson, F. Effect of the direction of DNA replication on mutagenesis by N-methyl-N′-nitro-N-nitrosoguanidine in adapted cells of Escherichia coli . Mol Gen Genet 208, 446–449 (1987). https://doi.org/10.1007/BF00328137
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00328137