Other pyrimidine dimers

Other pyrimidine dimers are known to result from far-UV irradiation in DNA. Homo- and hetero-dimers of cytosine have been observed. In this section, we discuss the characteristics of selected pyrimidine dimers. For this study we used the density functional theory (DFT) [31]. DFT is widely accepted now as providing accurate molecular structures and energetics. 

The geometries of T T, T C, CoT and C C and their radical cations were optimized with the 6-3IG basis set using the density functional method employing the Becke three parameter hybrid functional combined with the correlation functional of Lee, Yang and Parr (B3LYP) [32 - 34]. In this chapter we use the notation (base A) (base B) to indicate that the main chain (5 - 3 ) runs from base B to base A. 

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Formation of the photodimer is reversible, the dimer being split with high quantum yield with light of wavelength about 235 nm.(82> Similar dimerizations have been observed with several other pyrimidine derivatives, as... 

The effect of phase upon the monomer-dimer equilibrium is pronounced. The quantum yields for dimer formation in liquid-aerated water solution are low (from zero for thymine to 10"2 for other pyrimidines) but the quantum yields for dimer formation in frozen aqueous solutions or in single crystals are much higher (reaching unity in frozen water solution for thymine). The quantum yields for monomerization are uniformly high and are about the same in solution or in solid phase. The net result of this phase effect is that even at optimum wavelengths for dimer formation, the yields of dimers are low in solution and high in solid phases, for all the single bases, nucleosides, or nucleotides. 

Only the most general remarks will be made here about the photohydration reaction because, as in the case of dimerization phenomena, most experimental observations have been made on only single compounds and cannot be safely generalized to other pyrimidines. These will therefore be discussed under the headings of individual compounds and any general aspects mentioned at that time. Existing information about the hydration of pyrimidines is summarized in Table I. 

One obvious reason for the apparent lack of reaction of thymine in water is that the quantum yield for splitting of thymine dimer in solution is 0.5-1.0,28 independent of wavelength, and the probable yield for formation would not be higher, by analogy with other pyrimidines, than... 

However, although photolysis of dimethyluracil64 and of other pyrimidines may be genuinely oxygen independent, early observations of an oxygen effect on the rate of uracil photolyses have been confirmed (Sect. V) the kinetic evidence has been supplemented by the observation84 that dimer formation is almost entirely suppressed in oxygenated uracil solutions, and uracil hydrate is the whole product. This clear-cut... 

Virtually all forms of life are exposed to energy-rich radiation capable of causing chemical changes in DNA Near-UV radiation (with wavelengths of 200 to 400 nm), which makes up a significant portion of the solar spectrum, is known to cause pyrimidine dimer formation and other chemical changes in the DNA of bacteria and of... 

Abnormal bases (uracil, hypoxanthine, xanthine) alkylated bases in some other organisms, pyrimidine dimers... 

Most microorganisms have redundant pathways for the repair of cyclobutane pyrimidine dimers— making use of DNA photolyase and sometimes base-excision repair as alternatives to nucleotide-excision repair—but humans and other placental mammals do not. This lack of a back-up to nucleotide-excision repair for the removal of pyrimidine dimers has led to speculation that early mammalian evolution involved small, furry, nocturnal animals with little need to repair UV damage. However, mammals do have a path-... 

Pyrimidine dimers and other forms of DNA damage can be removed by a general excision repair mechanism. The first reaction in this form of repair involves forming nicks about the damaged region of the DNA. In (a) we see the mode of incision of UV-irradiated DNA by the pyrimidine-dimer-specific glycosylase and AP endonuclease... 

The purified E. coli protein has a molecular weight of 49 kD. It does not require any divalent cation for activity. It contains two different noncovalently bound chromophores that absorb light. One chromophore is flavin adenine dinucleotide (FADH- or FADH2). The other is 5,10-methenyltetrahydrofolyl polyglutamate (MTHF). The absorption of light by the chromophores is essential for the enzymatic reversal of the pyrimidine dimer back to the original pyrimidine monomers. However,... 

Nucleotide excision repair is the primary repair system for the removal of DNA damage caused by chemicals that produce bulky adducts or by the UV component of sunlight, which produces cyclobutane pyrimidine dimers (Pyr< >Pyr) and (6-4) photoproducts in DNA (1). These lesions, as well as other bulky lesions induced by chemical carcinogens, are removed by... 

The literature documents various situations in which C deamination is enhanced. These situations include the presence of C in cyclobutane pyrimidine dimers (a form of DNA damage caused by exposure to UV radiation see later discussion) or in mis-pairings with other bases or with alkylated bases (1). Cytosine deamination is also promoted in the presence of nitrons acid, a reaction that although not considered in this review, has lent much to our understanding of possible chemical mechanisms of spontaneous deamination (1). 

Ultraviolet light produces pyrimidine dimers in human DNA, as it does in E. coli DNA. Furthermore, the repair mechanisms are similar. Studies of skin fibroblasts from patients with xeroderma pigmentosum have revealed a biochemical defect in one form of this disease. In normal fibro-blasts, half the pyrimidine dimers produced by ultraviolet radiation are excised in less than 24 hours. In contrast, almost no dimers are excised in this time interval in fibroblasts derived from patients with xeroderma pigmentosum. The results of these studies show that xeroderma pigmentosum can be produced by a defect in the excinuclease that hydrolyzes the DNA backbone near a pyrimidine dimer. The drastic clinical consequences of this enzymatic defect emphasize the critical importance of DNA-repair processes. The disease can also be caused by mutations in eight other genes for DNA repair, which attests to the complexity of repair processes. 

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