Pyrimidine bases, photochemical dimerization

This knowledge regarding the efficient photochemical dimerization of the pyrimidine bases, led us to study, in detail, both the intramolecular... 

When DNA is exposed to radiation at wavelengths of about 260 nm, adjacent pyrimidines become covalently linked by the formation of a four-member ring structure resulting from the saturation of their respective C5, C6 double bonds. The structure formed by this photochemical cycloaddition is referred to as a pyrimidine dimer. The pyrimidine bases in DNA are thymine and cytosine. 

An unusual photochemical reaction of 2-pyridones, 2-aminopyridinium salts and pyran-2-ones is photodimerization to give the so-called butterfly dimers. These transformations are outlined in equations (13) and (14). Photodimerization by [2+2] cyclization is also a common and important reaction with these compounds. It has been the subject of particular study in pyrimidines, especially thymine, as irradiation of nucleic acids at ca. 260 nm effects photodimerization (e.g. equation 15) this in turn changes the regular hydrogen bonding pattern between bases on two chains and hence part of the double helix structure is disrupted. The dimerization is reversed if the DNA binds to an enzyme and this enzyme-DNA complex is irradiated at 300-500 nm. Many other examples of [2+2] photodimerization are known and it has recently been shown that 1,4-dithiin behaves similarly (equation 16) (82TL2651). 

An example of direct repair is the photochemical cleavage of pyrimidine dimers. Nearly all cells contain a photoreactivating enzyme called DNA photolyase. The E. coli enzyme, a 35-kd protein that contains bound N lO-methenyltetrahydrofolate and flavin adenine dinucleotide cofactors, binds to the distorted region of DNA. The enzyme uses light energy—specifically, the absorption of a photon by the N, N lO-methenyltetrahydrofolate coenzyme—to form an excited state that cleaves the dimer into its original bases. 

Two main UV lesions that form on DNA are cyclobutane pyrimidine dimers and 6-4 photoadducts. 6-4 photolyase uses reduced flavin to correct 6-4 photoadducts. DNA photolyases are flavoenzymes that photochemically reverse pyrimidine dimers formed in DNA by UV irradiation. DNA photolyases are monomeric proteins that have been divided into two classes based on sequence. " Class 1 enzymes are found in many microbes, while Class 2 enzymes have been found in higher organisms including goldfish and... 

EXAMPLE 8.14 DNA damage, in which bases acquire bulky substituents, or when they are displaced from their normal hydrogen-bonded positions, is remedied by nucleotide excision repair. A common example of such damage is formation of pyrimidine dimers. These form through photochemical reactions that are initiated by uthaviolet light. Carbon... 

Photochemical reactions of purines and pyrimidines in light are well known, and lead to mutations. Although various photochemical reactions can occur with both pyrimidines and purines, photodimerization of thymine is of the utmost importance. Photochemical reaction by UV irradiation of thymine results in formation of dimers with cyclobutane rings, which block DNA replication. Photodimerization was reported with the synthetic polymers having pendant thymine bases. In a study with polyacrylates and polymethacrylates with... 

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