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Complementary base pairing and the origin of substitution mutations

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Abstract

On the basis of chemical considerations and model building, the Watson–Crick concept of complementary base pairing is extended to a wider range of DNA pairs than A–T and G–C (including A–C, G–T, A–A, G–G and G–A) by invoking imino or enol tautomers (or protonated species) and syn isomers. The virtual absence of these additional base pairs from DNA is explained in terms of the low frequency with which these unfavoured forms occur and the two-step mechanism of DNA synthesis, whereby residues are first incorporated by the DNA polymerase and then checked. This base-pairing hypothesis is used to explain the origin, nature and level of spontaneous substitution mutations, their enhancement by base analogues, and the unique effects of certain mutator alleles.

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Authors and Affiliations

  1. Department of Biochemical Sciences, Princeton University, Princeton, New Jersey, 08540

    Michael D. Topal & Jacques R. Fresco

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  1. Michael D. Topal
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  2. Jacques R. Fresco
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Topal, M., Fresco, J. Complementary base pairing and the origin of substitution mutations. Nature 263, 285–289 (1976). https://doi.org/10.1038/263285a0

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  • DOI: https://doi.org/10.1038/263285a0

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