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Involvement of the mismatch repair system in base analogue-induced mutagenesis

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Summary

The influence of the mismatch repair system, and the role of mutS, mutR, and mutL genes, in mutagenesis induced by n2ome6Ade, n2oh6Ade and n2Pur have been investigated. From the frequency of reversion of Arg−Thr− and His− markers in AB2497, and its mut − derivatives, it was concluded that mismatches introduced by n2-ome6Ade and n2oh6Ade are better substrates for mismatch repair enzymes than that introduced by n2Pur. All these mut-gene products are more active in removing spontaneous or base analogue-induced mismatches which, when unexcised, lead to transversion of base pairs, than those which lead to transitions. Active engagements of mutL, mutR, or mutS gene products depend on the kind of mutation, the site of mutagenesis, and the inducing agent. Dam− cells are over-mutated by both n2ome6Ade and n2oh6Ade, but are hyper-sensitive to n2oh6Ade only. It is proposed that hyper-sensitivity of dam − cells is due not only to an increase in overlaping gap formation on both strands of DNA, but to a greater lability of the impaired cells.

Results are presented which strongly suggest that n2-ome6Ade in mut + cells and n2oh6Ade in mut − only, can induce GC→TA transversions.

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Abbreviations

n2ome6Ade:

2-amino-N6-methoxyadenine

n2-oh6Ade:

2-amino-N6-hydroxyadenine

n2Pur:

2-aminopurine

MMS:

methyl methanesulfonate

EMS:

ethyl methanesulfonate

MNNG:

N-methyl-N′-nitro-N-nitrosoguanidine

References

  • Bauer J, Krämmer G, Knippers R (1981) Asymetric repair of bacteriophage T7 heteroduplex DNA. Mol Gen Genet 181:541–547

    Google Scholar 

  • Coloundre C, Miller JH (1977) Genetic studies of the lac repressor. IV. Mutagenic specificity in the lacI gene of Escherichia coli. J Mol Biol 117:577–606

    Google Scholar 

  • Cox EC (1976) Bacterial mutator genes and control of spontaneous mutation. Annu Rev Genet 10:135–156

    Google Scholar 

  • Glickman BW, Van der Elsen P, Radman M (1978) Induced mutagenesis in dam − mutants of Escherichia coli: a role for 6-methyladenine in mutation evoidance. Mol Gen Genet 163:307–312

    Google Scholar 

  • Glickman BW, Radman M (1980) Escherichia coli mutator mutants deficient in methylation-instructed DNA mismatch correction. Proc Natl Acad Sci USA 77:1063–1067

    Google Scholar 

  • Janion C (1976) The synthesis and properties of N6-substituted 2-aminopurine derivatives. Acta Biochim Polon 23:57–68

    Google Scholar 

  • Jones M, Wagner R (1981) N-methyl-N′-nitro-N-nitrosoguanidine sensitivity of E. coli mutants deficient in DNA methylation and mismatch repair. Mol Gen Genet 184:562–563

    Google Scholar 

  • Karran P, Marinus MG (1982) Mismatch correction at O6-methylguanine residues in E. coli DNA. Nature 296:868–869

    Google Scholar 

  • Krych M, Pietrzykowska I, Szyszko J, Shugar D (1979) Genetic evidence for the nature, and excision repair of DNA lesions resulting from incorporation of 5-bromouracil. Mol Gen Genet 171:135–143

    Google Scholar 

  • Kushner SR, Shepherd J, Edwards G, Maples VF (1978) UvrD, uvrE, and recL represent a single gene. In: Hanawalt PC, Friedberg E, Fox CF (eds) DNA repair mechanism. Academic Press, Inc., New York, pp 251–254

    Google Scholar 

  • Maenhaut-Michel G, Caillet-Fauquet P (1982a) Effects of Escherichia coli mutator genes mutH, mutL and mutS on 2-aminopurine induced DNA repair. Biochemie 64:739–742

    Google Scholar 

  • Maenhaut-Michel G, Caillet-Fauquet P (1982b) 2-aminopurine induced DNA repair in E. coli. Mol Gen Genet 188:143–148

    Google Scholar 

  • Marinus MG, Morris R (1974) Biological function for the 6-methyladenine residues in the DNA of Escherichia coli K12. J Mol Biol:309–322

  • Marinus MG, Morris R (1975) Pleiotropic effects of a DNA adenine methylation mutation (dam-3) in Escherichia coli K12. Mutat Res 28:15–26

    Google Scholar 

  • Mayer VM, Gadbridge MG, Oswald EJ (1969) Rapid plate test for evaluating phage induction capacity. Appl Microbiol 18:697–698

    Google Scholar 

  • Miller JH (1972) Experiments in molecular genetics. Cold Spring Harbor Laboratory, New York

    Google Scholar 

  • Mohn GR, Guijt N, Glickman BW (1980) Influence of DNA adenine methylation dam mutation and of plasmid pKM101 on the spontaneous and induced mutability of certain genes in Escherichia coli K12. Mutat Res 74:255–265

    Google Scholar 

  • Nevers P, Spatz H (1975) Escherichia coli mutants uvrD and uvrE deficient in gene conversion of λ-heteroduplexes. Mol Gen Genet 139:133–143

    Google Scholar 

  • Persing DH, McGinty L, Adams CW, Fowler RG (1981) Mutational specificity of the base analogue, 2-aminopurine, in Escherichia coli. Mutat Res 83:25–37

    Google Scholar 

  • Radman M, Dohet C, Bourguignon M-F, Dobleday BP, Lecomte P (1981) High fidelity devices in the reproduction of DNA. In: Seeberg E, Kleppe K (eds) Chromosome demage and repair. Plenum Publishing Corp, New York, pp 431–445

    Google Scholar 

  • Radman M, Villani G, Boiteux S, Kinsella AR, Glickman BW, Spadari S (1979) Replicational fidelity: mechanism of mutation avoidance and mutation fixation. Cold Spring Harbor Symp Quant Biol 43:937–946

    Google Scholar 

  • Radman M, Wagner RE Jr, Glickman BW, Meselson M (1980) In: Alàcević M (ed) Progress in environmental mutagenesis. Elsevier/North Holland Biomedical Press, Amsterdam, pp 121–130

    Google Scholar 

  • Rydberg B (1977) Bromouracil mutagenesis in Escherichia coli: Evidence for involvement of mismatch repair. Mol Gen Genet 152:19–28

    Google Scholar 

  • Rydberg B (1978) Bromouracil mutagenesis and mismatch repair in mutator strains of Escherichia coli. Mutat Res 52:11–24

    Google Scholar 

  • Sledziewska-Gójska E, Janion C (1982) Effect of proof-reading and dam-instructed mismatch repair systems on N4-hydroxycytidine-induced mutagenesis. Mol Gen Genet 186:411–418

    Google Scholar 

  • Szyszko J, Pietrzykowska I, Twardowski T, Shugar D (1983) Identification of uracil as a major lesion in E. coli DNA following the incorporation of 5-bromouracil, and some of the accompanying effects. Mutat Res 108:13–27

    Google Scholar 

  • Todd PA, Monti-Bragadin C, Glickman BW (1979) MMS mutagenesis in strains of Escherichia coli carrying the R46 mutagenic enhancing plasmid: Phenotypic analysis of Arg+ revertants. Mutat Res 62:227–237

    Google Scholar 

  • Vogel HJ, Bonner DM (1956) Acetyloornithinase of Escherichia coli, partial purification and some properties. J Biol Chem 218:97–106

    Google Scholar 

  • Wagner R Jr, Meselson M (1976) Repair tracts in mismatches DNA heteroduplexes. Proc Natl Acad Sci USA 73:4135–4139

    Google Scholar 

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Authors and Affiliations

  1. Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Rakowiecka 36, PL-02-532, Warszawa, Poland

    Katarzyna Bebenek & Celina Janion

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  1. Katarzyna Bebenek
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  2. Celina Janion
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Communicated by D.M. Goldfarb

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Bebenek, K., Janion, C. Involvement of the mismatch repair system in base analogue-induced mutagenesis. Mol Gen Genet 191, 276–281 (1983). https://doi.org/10.1007/BF00334826

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