Pyrimidine Bases In DNA Research Articles

Light scattering and viscosimetric studies on DNA after the photoreaction with some furocoumarins.

The light scattering measurements and the viscosimetric “i-assay” performed on native DNA solutions before and after irradiation at 3655 Å in the presence of furocoumarins show that the C4-cycloadditions of furocoumarins to the 5,6-double bond of the pyrimidine bases of DNA, which take place in the photoreactions, produce neither breakages of the polynucleotide chains nor relevant modifications of the macromolecule conformation.

Electron aspects of the mode of action of the mitomycin molecule

Mitomycins are unique antibiotics, as they include an aziridine ring. According to recent experimental results, they are completely inert in their native form and are activated by a reductive process which results in the extension of a π-electron system in their molecular structures. In the present article, the stability and sensitivity of the aziridine ring in pre- and post-activation reactions are explained by considering the various electronic effects to that ring. Then a conception of an intermediary semiquinoid form of activated mitomycin is introduced. In particular, the stability and reactivity of this ionized radical form is analysed from the standpoint of established resonance theory. In parallel with this analysis, some electronic features of the purine and pyrimidine bases in DNA are examined. As a natural result of the combination of these analyses, the electronic mechanism of cross-linkage formation of the mitomycin molecule between the complementary strands of DNA is interpreted. Further, the preferential contribution of cytosine and guanine components to the cross-link formation, predicted experimentally, is explained by considering how easily tautomerism can occur. The promoting effect of deoxycytidilic acid to the cross-linking reaction of mitomycin in the reductive medium is also interpreted on the basis of tautomeric isomerism of cytosine and the semiquinoid formation of activated mitomycin.

Structural requirements for the binding of ethidium to nucleic acids

1. 1. Ethidium bromide, a phenanthridine drug, forms soluble metachromatic complexes with nucleic acids. The mechanism of the interaction has been investigated by studying the ability of substances related to nucleic acids to shift the visible absorption band of the drug in solution. 2. Purine and pyrimidine nucleotides produce slight shifts to longer wavelengths and the purine compounds are the more effective. However, neither purine nor pyrimidine bases in DNA act as specific binding sites for the drug since complete removal of either type of base from DNA leads to diminished interaction. 3. Although ethidium forms metachromatic complexes with homopolymers, binding curves indicate that the interaction with these materials is quite different from the strong primary binding seen with DNA or RNA. The curves suggest a facilitated binding process which probably represents the weaker secondary binding to nucleic acids. 4. From measurements of the interaction between ethidium and mixtures of homopolymers a correlation is described between the ability of synthetic polynucleotides to bind the drug strongly and the possession of base-paired helical structure. The helical structure need not necessarily be stabilised by purine-pyrimidine contacts. 5. These results provide further evidence that the primary binding of ethidium to nucleic acids occurs by a process of intercalation between adjacent base-pairs while secondary binding occurs by a “stacking” mechanism.

On the mechanism of ultraviolet-induced mutations

Calculations based on the Huckel molecular-orbital method were made of excited states induced by ultraviolet radiation for the purine and pyrimidine bases of DNA. Data are presented for uracil, thymine, guanine, cytosine, and adenine. It is postulated that the ease of tautomeric transformations of these compounds in their excited states may account in part for the enhancing effect of ultraviolet radiation on the rate of mutagenesis. (C.H.)

Disappearance of thymine photodimer in ultraviolet irradiated DNA upon treatment with a photoreactivating enzyme from Baker's yeast

Fifty years ago thymine dimer was discovered in the Biochemical and Biophysical Laboratory of Delft Technological University, The Netherlands, by one of the authors of this review (Beukers) as the first environmentally induced DNA lesion. It is one of the photoproducts formed between adjacent pyrimidine bases in DNA by UV irradiation, currently known as cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts. Major lesions found in DNA after in vitro or in vivo UV irradiation are the cis–syn cyclobutane thymine dimer and the thymine–cytosine (6-4) photoproduct. Even after 50 years the study of photo-induced DNA lesions is still going on as is illustrated by the hundreds of papers published every year and the millions hits when browsing the internet for dimer-related information.Living organisms possess efficient and different mechanisms to repair detrimental lesions in their DNA. A unique mechanism to repair CPDs is reversion by either direct interaction with light of short wavelength or by enzymatic photoreactivation. Photophysical mechanisms that induce and reverse molecular bonds in biological macromolecules have been a main focus of research of the group in Delft in the middle of the last century. This review describes the break-through results of these studies which were the result of intense interactions between scientists in the fields of physics, organic chemistry and biochemistry. Philosophically, the “view” of the group in Delft was very appealing: since in nature photolesions are induced in DNA by the sun, how is it possible that repair of these lesions could be accomplished by the same energy source. Evolutionary, it is hardly possible to think of a more efficient repair mechanism.