Disease relevance of thymine

• Ultraviolet irradiation forms covalent crosslinks between E. coli RNA polymerase and the lac UV5 promoter substituted with bromouracil in the place of thymine [1].
• McArdle's disease is genetically heterogeneous, but the most common mutation is the substitution of thymine for cytosine at codon 49 [2].
• The linkages are susceptible to direct photoreversal by 254 nm UV, as expected for cyclobutane-type thymine dimers, but they are not cleaved by the bacteriophage T4 endonuclease V, a dimer-specific DNA repair enzyme [3].
• Excision of thymine dimers from specifically incised DNA by extracts of xeroderma pigmentosum cells [4].
• In 24 (69%) of the 35 papillary thyroid carcinomas examined, we found a missense thymine (T)-->adenine (A) transversion at nucleotide 1796 in the BRAF gene (T1796A) [5].

Psychiatry related information on thymine

• The reactivity of FCDI with the guanine bases was smaller than that with the thymine ones and the prolongation of the reaction time resulted in a lower yield [6].
• Our previous study suggested that the tumour necrosis factor-alpha gene with thymine residue at position -857 in its promoter region [TNF-alpha(-857T)] could be associated with human narcolepsy independently of a strong association of the human leucocyte antigen (HLA)-DRB1*1501 with the disorder [7].

High impact information on thymine

• Dpo4 is also captured in the crystal translocating two template bases to the active site at once, suggesting a possible mechanism for bypassing thymine dimers [8].
• Vertebrate genomic DNA is generally CpG depleted, possibly because methylation of cytosines at 80% of CpG dinucleotides results in their frequent mutation to thymine, and thus CpG to TpG dinucleotides [9].
• In E. coli, the enzyme recognizes a TG mismatched base pair, generated after spontaneous deamination of methylated cytosines, and cleaves the phosphate backbone on the 5' side of the thymine [10].
• Analysis of 347 plaques obtained after transfection of this modified DNA indicated that mispairs were corrected in 343 cases (99%), revealing 314 repair events in favor of guanine (90%) and 29 in favor of thymine (8%) [11].
• The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites [12].

Chemical compound and disease context of thymine

• Nonpolar DNA base shape mimics of thymine and adenine (abbreviated F and Q, respectively) were introduced into Escherichia coli by insertion into a phage genome followed by transfection of the vector into bacteria [13].
• Amplification of this library in a dut ung strain of Escherichia coli allowed the recovery of the library as closed circular single-stranded DNA with uracil frequently incorporated in place of thymine [14].
• The mutational specificity and genetic requirements for mutagenesis by 5,6-dihydroxy-5,6-dihydrothymine (thymine glycol), one of the principal DNA lesions induced by oxidation and ionizing radiation, has been investigated in Escherichia coli [15].
• Studies were undertaken to determine how a line of mutant Syrian hamster melanoma cells (HAB-2E) that displays unlimited growth potential when all of the thymine residues in nuclear DNA are replaced by bromouracil (BrUra) could avoid the deleterious effects of bromodeoxyuridine (BrdUrd) mutagenicity [16].
• When expressed in E. coli, the NTG1 gene product cleaves plasmid DNA damaged by osmium tetroxide, thus, indicating specificity for thymine glycols in DNA similarly as is the case for EndoIII [17].

Biological context of thymine

• TFIID binding shows phosphate contacts with the same residues that were found to be essential for TFIID interactions by methylation and thymine-specific modification interference assays [18].
• Age-dependent excision repair of damaged thymine from gamma-irradiated DNA by isolated nuclei from human fibroblasts [19].
• Hydrolytic deamination of 5-methylcytosine bases in DNA leads to thymine residues, and hence to T/G mismatches, pre-mutagenic DNA lesions consisting of two natural DNA constituents and thus devoid of an obvious marker of the damaged DNA strand [20].
• Recombinant human DNA polymerase eta corrects the inability of XP-V cell extracts to carry out DNA replication by bypassing thymine dimers on damaged DNA [21].
• We report here that thymidine oligonucleotides annealed to polydeoxyadenylate can be ligated end-to-end by UV irradiation, via thymine dimerization of the terminal nucleotides in adjacent oligonucleotides [3].

Anatomical context of thymine

• Using an improved cell-free assay for trans-lesion DNA synthesis, we have recently isolated a DNA polymerase from HeLa cells that continues replication on damaged DNA by bypassing ultraviolet-induced thymine dimers in XP-V cell extracts [21].
• Induction and repair of thymine glycols were studied in irradiated A549 cells (a human lung carcinoma cell line) [22].
• Since 1971 thymine-requiring (thy-) pathogens have been isolated from the urine of 8 patients with renal calculi, and from the sputum of 1 patient with chronic chest infection [23].
• Crude extracts of normal human diploid fibroblasts and of human peripheral blood lymphocytes excise thymine dimers from purified ultraviolet-irradiated DNA, or from the DNA presumably present as chromatin in unfractionated cell-free preparations of cells that had been labeled with [3H]thymidine [24].
• Thymine glycols were produced in DNA in a dose-dependent manner after exposure of human mammary epithelial cells to benzo[a]pyrene [25].

Associations of thymine with other chemical compounds

• These results indicate that this replacement of thymine by uracil in DNA does not seriously impair the biological functionality of T4 DNA, provided the DNA is not subjected to the breakdown (repair) pathway initiated by uracil--DNA glycosidase [26].
• With the DNA in solution, the repeating polymer poly[d(G-C)] - poly[d((G-C)] (where G is guanine and C is cytosine) enhanced the fluorescence of olivomycin, while the antibotic fluorescence was not affected by the alternating polynucleotide poly]d(A-T)] - poly[d(A-T)] (where A is adenine and T is thymine) [27].
• The gene is unusual in that its base composition is nearly 90 percent adenine plus thymine [28].
• The strong binding sites for echinomycin contain the central two-base-pair sequence 5'-CG-3'. From an analysis of 15 echinomycin sites on 210 base pairs of DNA, key recognition elements for echinomycin are contained in the sequences (5'-3') ACGT and TCGT (A, adenine; C, cytosine; G, guanine; T, thymine) [29].
• Yeast DNA polymerase zeta (zeta) is essential for error-free replication past thymine glycol [30].
• The theoretical study suggests that radical anion 3, in which the spin density and charge distribution are located in both thymine rings, undergoes a fast partially ionic splitting of the cyclobutane with a half-life of a few ps [31].

Gene context of thymine

• This structure indicates a more invasive interaction with dsDNA than observed with other UDGs and reveals an elegant water displacement/replacement mechanism that allows SMUG1 to exclude thymine from its active site while accepting HmU [32].
• DME and ROS1 show a preference for 5-meC over thymine in the symmetric dinucleotide CpG context, where most plant DNA methylation occurs [33].
• The ER mutant HE84, which contains a single amino acid exchange, Glu-203 to Gly, in the knuckle of ER, creates a promiscuous ER that is able to bind to GRE/PREs by contacting this thymine [34].
• Using reverse transcription-PCR, single-strand conformational polymorphism, and sequencing analysis, the COOH-terminal domain of SMAD4 was found to be mutated: a single thymine was inserted between nt 1521 and 1522 in 2 of 20 tumors analyzed [35].
• Mismatch repair in methylated DNA. Structure and activity of the mismatch-specific thymine glycosylase domain of methyl-CpG-binding protein MBD4 [36].

Analytical, diagnostic and therapeutic context of thymine

• In an attempt to find a noninvasive assay for oxidative DNA damage in individuals, we have developed an HPLC assay for free thymine glycol and thymidine glycol in urine [37].
• Genetic effects of thymine glycol: site-specific mutagenesis and molecular modeling studies [15].
• Direct measurement of thymine dimers and (6-4) photoproducts by immunoassay demonstrates faster repair of both of these UV-induced photoproducts in pTpT-treated fibroblasts [38].
• Polymerase chain reaction (PCR)-based sequence analysis showed that the propositus' gene for HCII (HCII Awaji gene) had a thymine insertion after codon (GAT) for Asp88 in exon II, resulting in a frameshift mutation [39].
• The method uses bisulfite-modified DNA as a template for PCR amplification, resulting in conversion of unmethylated cytosine, but not methylated cytosine, into thymine within CpG islands of interest [40].

References