Physical changes and mutagenesis

Mistakes, in a repair mechanism, that are associated with the replacement of structurally incorrect regions in DNA by normal bases will be discussed as possible causes of mutagenesis.

Abstract

Ultraviolet irradiation of DNA in vitro and in vivo results in the formation of a known structural change — the dimerization of adjacent thymines in the same polynucleotide chain. Many lines of evidence indicate that thymine dimers are responsible for a major part of the lethal, and perhaps mutagenic, effects of ultraviolet irradiation. For example: dimers are split by short-wavelength ultraviolet and by enzymic action in the presence of visible light; and the decrease in the number of dimers is well correlated with the observed increase in biological activity of DNA or increase in colony-forming ability of ultraviolet-irradiated cells. The obvious result of dimer formation is the blockage of DNA synthesis. Studies on an in vitro polymerase system indicate that, in the slow polymerization around thymine dimers, bases other than A are incorporated and that the polymerase product is not complementary to the primer. In cells of Escherichia coli, on the other hand, the major way of coping with the dimers is to remove them from the bacterial DNA in the form of small oligonucleotides. Such an error-correcting mechanism would be expected to work for all changes that affect the hydrogen bonding of normal DNA. Mistakes, in a repair mechanism, that are associated with the replacement of structurally incorrect regions in DNA by normal bases will be discussed as possible causes of mutagenesis.