"The theory of mutagenesis"

Date:
1961
Reference:
PP/CRI/H/3/3
Catalogue details

Licence: In copyright

Credit: "The theory of mutagenesis". Source: Wellcome Collection.

    3/7
    it was already in the DNA. Such alterations only change a purine into another purine, or a pyrimidine into another pyrimidine. Breese (1959b) has called these transitions. He suggested that other conceivable changes, which he called transversions (such as, for example, from A T to C G) which change a purine into a pyrimidine and vice versa, occurred during mutagenesis by proflavin. This would neatly account for the two mutually exclusive classes of mutagens, since it is easy to see that a transition cannot be reversed by a transversion, and vice versa. We have been led to doubt this explanation for the following reasons. Our suspicions were first aroused by the curious fact that a comparison between the sites of mutation for one set of mutants made with BD and another set made with PB (Brenner, Benzer and Barnett, 1958) showed there were no sites in the r^ gene, among the samples studied, common to both groups. Now this result alone need not be incompatible with Breese's theory of mutagenesis, since we have no good explanation for hot spots and this confuses quantitative argument. However it led us to the following hypothesis? that acridines act as mutagens because they cause the insertion or the deletion of a base pair . This idea springs rather naturally from the views of Lerman (in manuscript) and Luzzati (in preparation) that acridines are bound to DNA by sliding between adjacent base- pairs, thus forcing them 6.8 A apart, rather than 3.+ A. If this occasionally happened between the bases on one chain of the DNA, but not the other, during replication, it might easily lead to the addition or subtraction of a base. Such a possible mechanism leads to a prediction. Vie know practically nothing about coding (Grick, 1959) but on most theories (except overlapping codes which are discredited because of criticism by Brenner (1957)) the deletion or the addition of a base pair is likely to cause not the substitution of just one amino acid for another, but a much more substantial alteration, such as a break in the polypeptide chain, a considerable alteration of the amino acid sequence, or the production of no protein at all.
    digitised image 1
    digitised image 2
    digitised image 3