Thymine formation from uracil

A common source of DNA damage is the spontaneous loss of the amine group on cytosine and the formation of an amide. This occurs at a rate of about 100 times a day. Fortunately, the body produces enzymes able to detect and repair such degraded cytosines. Given this information, suggest why DNA differs from RNA in possessing the nucleotide thymine rather than uracil. 

Daniels352 has shown that the excitation spectra for triplet state formation and fluorescence emission from uracil and thymine in neutral aqueous solution at room temperature were anomalous when compared with the UV absorption spectra of these pyrimidines. These experimental facts have been critically examined with respect to three molecular models, of which the model based on tautomerism of uracil in aqueous solution is, in the opinion of Daniels, the best. The data suggested that the fluorescing tautomer contained an enol group, and the UV data favored the 4-hydroxy structure, i.e., form 28. The second tautomer, from which the triplet originated, was expected to be the predominant diketo form (32). 

The answer is a. (Murray, pp 627-661. Scriver, pp 3897-3964. Sack, pp 121-138. Wilson, pp 287—320.) The structure shown in the question is the vitamin tolic acid. Tetrahydrofolic acid, the active cofactor derived from lolic acid, is required in two steps of purine synthesis and thus required in the de novo synthesis of ATP and GTE CTP and TTP are pyrimidine base derivatives, and although de novo synthesis of the pyrimidine ring does not require tetrahydrofolate, the formation of thymine from uracil does. NADH and NADPH require niacin for their synthesis. 

The methylation of dUMP by thymidylate synthetase is mediated by tetrahydrofolate and required for the formation of dTMP. Its loss by mutation creates a thymine-requiring auxotroph [127-129], Another alternate path for the synthesis of dTTP has been revealed by the use of the multimutational cytidine auxotrophs described above. Differential labeling of cytidine and uracil precursors in both E. coli [126] and Salmonella [125] shows that dTTP arises independently from either. Indeed, the contribution from cytidine is three to four times that from uracil. It is suggested that the second path involves a methylation of dCTP, then a deamination to give dTTP. One wonders why this pathway is not available in the thymine-requiring mutants which lack TMP synthetase. One explanation is that TMP synthetase may also function for the methylation of dCTP however, this has not yet been found to serve as an alternate substrate [130]. Two pathways may indeed exist in B. suhtilis, as indicated by the fact that two separate mutations are needed to obtain a thymine-requiring mutant [131]. 

In contrast, the photochemistry of uracil, thymine and related bases has a large and detailed literature because most of the adverse effects produced by UV irradiation of tissues seem to result from dimer formation involving adjacent thymine residues in DNA. Three types of reaction are recognizable (i) photohydration of uracil but not thymine (see Section 2.13.2.1.2), (ii) the oxidation of both bases during irradiation and (iii) photodimer formation. 

Lehn and Rotello s groups extensively studied diacyldiaminopyridines that form triple hydrogen bonded associated structures with uracil and thymine groups (Gulik-Krzywicki et al. 1993 Carroll et al. 2003 Stubbs and Week 2003 Sanyal et al. 2004). lUian et al. (2000) studied the formation of vesicles from mixtures of randomly functionalized complementary copolymers containing thymine groups and... 

A number of studies on photochemistry of the nucleic acid bases in aqueous solutions demonstrated that while uracil undergoes reversible hydration under exposure to UV irradiation, the other bases (thymine, adenine, and guanine) were stable [41,42], However, the sensitivity of dissolved thymine to UV irradiation can be significantly increased if the solution is rapidly frozen [43]. In 1960 the thymine photoproduct was isolated from irradiated frozen aqueous solution of thymine. Elemental analysis, molecular weight measurements, powder X-ray diffraction, NMR and IR spectroscopy confirmed that the most likely photoproduct is a thymine dimer [20]. Similar photoproduct was obtained by hydrolysis of irradiated DNA. Its formation was attributed to reaction between two adjacent thymine groups on the same DNA chain [44], Independently an identical compound was isolated from DNA of UV-irradiated bacteria [45]. 

---