Spectrum of N4-aminocytidine mutagenesis

Tadayoshi Bessho, Keiko Matsumoto, Akinori Nomura, Hikoya Hayatsu, Kazuo Negishi

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Abstract

N4-Aminocytidine, a nucleoside analog, is a potent mutagen towards phages, bacteria, Drosophila and mammalian cells in culture. In vitro, biochemical studies indicate that this reagent acts by being incorporated into DNA. To elucidate the mechanism of N4-aminocytidine mutagenesis, it is essential to identify the nature of DNA sequence alterations taking place during the mutagenesis. We have analyzed the nucleotide sequence changes in the lac promoter-lacZα region of M13mp2 phage induced by treatment of phage-infected Escherichia coli with N4-aminocytidine. The sequence alterations of DNA samples from 89 mutants of the phage were determined. These mutants had single point mutations, except one mutant, in which a double point mutation was detected. Several hot spots were found: however, there are no apparent relations to particular DNA sequences regarding the locations of these spots. All the mutations are transitions; neither transversions nor deletions/insertions were found. A feature in these transitions is that the A/T to G/C and G/C to A/T changes occur at approximately equal rates. The overall picture of the mutagenesis is consistent with a scheme in which misincorporation and misreplication caused by the modified cytosine structure are the key steps in the DNA replication leading to transitions. Similar nucleotide alterations were found for the mutagenesis induced by an alkylated derivative, N′-methyl-N4-arninocytidine. N4-Aminocytidine also induced reversions of these mutants; both A/T to G/C and G/C to A/T transitions again took place.

Original languageEnglish (US)
Pages (from-to)659-664
Number of pages6
JournalJournal of Molecular Biology
Volume205
Issue number4
DOIs
StatePublished - Feb 20 1989

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ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Bessho, T., Matsumoto, K., Nomura, A., Hayatsu, H., & Negishi, K. (1989). Spectrum of N4-aminocytidine mutagenesis. Journal of Molecular Biology, 205(4), 659-664. https://doi.org/10.1016/0022-2836(89)90311-2