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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Oct;81(20):6271–6275. doi: 10.1073/pnas.81.20.6271

In vivo mutagenesis by O6-methylguanine built into a unique site in a viral genome.

E L Loechler, C L Green, J M Essigmann
PMCID: PMC391905  PMID: 6093094

Abstract

The mutagenicity of O6-methylguanine (O6MeGua), a chemical carcinogen-DNA adduct, has been studied in vivo by using a single-stranded M13mp8 genome in which a single O6MeGua residue was positioned in the unique recognition site for the restriction endonuclease Pst I. Transformation of Escherichia coli MM294A cells with this vector gave progeny phage, of which 0.4% were mutated in their Pst I site. In a separate experiment, cellular levels of O6MeGua-DNA methyltransferase (an O6MeGua-repair protein) were depleted by treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) prior to viral DNA uptake. In these cells, the mutation frequency due to O6MeGua increased with increasing MNNG dose (the highest mutation frequency observed was 20%). DNA sequence analysis of 60 mutant genomes revealed that O6MeGua induced exclusively G-to-A transitions.

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Selected References

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