Cyclobutyl dimer

J.C. Sutherland and Griffin incorporated tritium-labelled thymine into DNA and irradiated it with 313 nm light in buffered saline in the presence of p-aminobenzoic acid for up to 12 min. After separation of the products by TLC, the radioactivity was associated with a fraction which had the characteristic RF of dimers. When the hydrolysate from a 313 nm irradiated sample was re-irradiated at 254 nm and then chromatographed, the radioactivity had the mobility of thymine monomer. This is characteristic of pyrimidine cyclobutyl dimers which were known to be photosynthesized at 313 nm and photodegrad-ed to monomers at 254 nm. Although not degraded itself, the p-aminobenzoic acid clearly acted as a photosensitizer for the DNA-damaging thymine dimerization [40]. 

The antidepressant protriptyline (116) causes skin photosensitization in man. Jones and Sharpies irradiated an aqueous solution of the hydrochloride with a medium-pressure mercury lamp for 16 h and separated the products by preparative TLC. First formed was the epoxide (117) which photohydrated to the diol (118). Also isolated was the enol (119) [84], Earlier, Gasparro and Kochevar had shown that only the hydrochloride was photodegraded under nitrogen in water or ethanol. Three products were isolated and all lysed erythrocytes, but the structure of only one was suggested. This was a cyclobutyl dimer as shown by its mass spectrum and its photolysis back to protriptyline by light of 254 nm. Presumably, a [2 + 2] cycloaddition of the olefine bonds had occurred [85]. 

Yeh and Falvey 1991). However, the cyclobutyl dimer of a quinone, and a dithymoquinone, also cleaves on single-electron rednction but much slower than the pyrimidine dimers (Robbins and Falvey 1993). It is truly an unresolved issue as to why the anion-radical cleavage depicted in Scheme 3.72 is so facile. Water participation can probably decrease the barrier of the cycloreversion on physiological conditions (Saettel and Wiest 2001, 2006). Besides, hydration effect is known to increase the electron affinities of nucleic bases (Scheidt et al. 1998, Kim and Schaefer 2007a, 2007b). 

Gibbs, P.E., McDonald, J., Woodgate, R., and Lawrence, C.W. (2005) The relative roles in vivo of Saccharomyces cerevisiae Pol q, Pol Revl protein and Pol32 in the bypass and mutation induction of an abasic site, T-T (6-4) photoadduct and T-T cis-syn cyclobutyl dimer. Genetics, 169, 575-582. 

Kang, H.-S., Hidema, J., and Kumagai, T., Effects of light environment during culture on UV-induced cyclobutyl pyrimidine dimers and their photorepair in rice Oryza sativa L.),... 

For R2 = cyclobutyl the results are not very much different from those for R = alkyl207. The substitution of one of the alkyl groups by Cp(CO)2Fe leads to the formation of the dimer only when the remaining alkyl group is methyl. The proposed intermediate silene may be trapped by dienes like DMB or Cp208. 

J.J. Chen, C.Z, Jiang, A.B. Britt (1996). Little or no repair of cyclobutyl pyrimidine dimers is observed in the organellar genomes of the young Arabidopsis seedling. Plant Physiol, 111, 19-25. 

Another common type of DNA damage is due to the formation of thymine dimers induced by ultraviolet and ionizing radiation. These intrastrand covalent bonds form a cyclobutyl ring between the C-5 and C-6 of one thymine, and the same carbons on the adjacent thymine. The result is that the DNA backbone on the thymine-containing strand is structurally altered, which may cause disruption of the hydrogen bonds with the corresponding adenine residues on the complementary strand (Fig. 23.2.). 

The removal of thymine dimers by nucleotide excision repair is shown in Figure 23.3. This is sometimes called bulky lesion repair because the structure recognized by the DNA repair enzymes is an abnormality in the DNA backbone, such as would result from the formation of the cyclobutyl ring in a thymine dimer (see Fig. 23.2). 

FIGURE 8-34 Formation of pyrimidine dimers induced by UV iight. (a) One type of reaction (on the left) results in the formation of a cyclobutyl ring involving C-5 and C-6 of adjacent pyrimidine residues. An alternative reaction (on the right) results in a 6-4 photoproduct, with a linkage between C-6 of one pyrimidine and C-4 of its neighbor, (b) Formation of a cyclobutane pyrimidine dimer introduces a bend or kink into the DNA. 

FIGURE 10.12 UV irradiation causes dimerization of adjacent thymine bases. A cyclobutyl ring is formed between carbons 5 and 6 of the pyrimidine rings. Normal base pairing is disrupted by the presence of such dimers. 

Costalat, R., Blais, J., Ballini, J.-R, Moysan, A., Cadet, J., Chalvet, O., and Vigny, R, Formation of cyclobutyl thymine dimers photosensitized by pyridopsoralens a triplet-triplet energy transfer mechanism, Photochem. Photobiol, 51, 255, 1990. 

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