Disease relevance of thymidylic acid

• I-TevI, the intron-encoded endonuclease from the thymidylate synthase (td) gene of bacteriophage T4, binds its DNA substrate across the minor groove in a sequence-tolerant fashion [1].
• Rapid characterization of the variable length polythymidine tract in the cystic fibrosis (CFTR) gene: association of the 5T allele with selected CFTR mutations and its incidence in atypical sinopulmonary disease [2].
• The specificity of a factor-dependent translation system of Escherichia coli was shown to change according to the principle: "either ribo- or deoxyribopolynucleotide messenger". Poly(dT) is shown to be effectively translated in the absence of elongation factors, both at low (2 degrees C) and high (37 degrees C) temperature [3].
• These data suggest that the 5T polythymidine tract sequence on specific haplotype backgrounds (TG12 and M470V) may cause a low level of full-length functional CFTR protein and CF-like lung disease [4].
• Effective utilization of exogenous deoxythymidine-5'-monophosphate for DNA synthesis in enterobacteria [5].

High impact information on thymidylic acid

• We found an inverse relationship between the length of the polythymidine tract at the exon 9 splice branch/acceptor site and the proportion of exon 9- CFTR mRNA transcripts [6].
• In situ cleavage assays and phasing analyses indicate that upon nicking the bottom strand of the td homing site, I-TevI induces a directed bend of 38 degrees towards the major groove near the cleavage site [1].
• We demonstrate here that the 28 kDa I-TevI binds the extensive 37 bp td homing site as a monomer and significantly distorts its substrate [1].
• We measured 20 different hairpin sequences with quasi-random stem sequences that were 6-30 bp long, polythymidine loops that were 3-30 nt long, and stem GC content that ranged from 0% to 100% [7].
• The 1016-base-pair (bp) intron in the T4 bacteriophage thymidylate synthase gene (td) contains a 735-bp open reading frame that encodes a protein product with endonucleolytic activity [8].

Biological context of thymidylic acid

• Exon 9 alternative splicing is modulated by a polymorphic polythymidine tract within its 3' splice site [9].
• The plasmid SSB-like proteins show the highest affinity for polydeoxythymidylic acid; these complexes are the least sensitive to disruption by salt [10].
• Polythymidine alleles were identified for mutations either associated with a wide range of clinical phenotypes (R117H, R347P, G85E, D1152H, R334W, 2789 + 5 G > A, 3849 + 10kb C > T), and/or located at hypermutable CpG loci (R117H, 3845 + 10kb C > T, R553X, R334W, S945L and R75Q) [2].
• Thymidylate synthetase (TS) is known to catalyse the methylation of deoxyuridine monophosphate (dUMP) for the de novo synthesis of deoxythymidine monophosphate (dTMP) [11].
• Another common polymorphism of the CFTR gene has recently been implicated in the pathogenesis of idiopathic chronic pancreatitis, the 5T variant of the variable length polythymidine tract in intron 8 (the normal genotypes are 7T and 9T) [12].

Anatomical context of thymidylic acid

• Covalent attachment of polydeoxythymidylic acid to human erythrocytes [13].
• Poly(dT) inhibition of globin synthesis in the rabbit reticulocyte lysate system. Reversal of the inhibition by poly(dT)-binding protein [14].

Associations of thymidylic acid with other chemical compounds

• A discrete class of strains of Saccharomyces cerevisiae, able to utilize, highly efficiently, exogenous deoxythymidine-5'-monophosphate (dTMP),was found to be sensitive to concentrations greater than 10 Micro M dTMP in an otherwise complete growth medium [15].
• BACKGROUND: Thymidylate synthase (TS) catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) and is a key enzyme for DNA synthesis [16].
• The TS enzymatic mechanism involves the reductive methylation of the substrate, deoxyuridine monophosphate (dUMP), by transfer of a methylene group from the co-factor, methylenetetrahydrofolate (CH2H4folate), resulting in the production of deoxythymidine monophosphate (dTMP) and dihydrofolate (H2folate) [17].
• Radiation-generated hydroxyl radicals and hydrogen atoms were shown to induce the cross-linking of polydeoxythymidylic acid (mol X wt approximately 170 000) in N2O-saturated acqueous solution [18].

Gene context of thymidylic acid

• The endonuclease shows specificity for the intronless form of the td gene [8].
• This partially purified preparation has been found to contain a DNA endonuclease activity specific for the td delta I gene, which contains a precise deletion of the intron [19].
• Furthermore, the spin-labeled nucleotide was found to be incorporated internally into polydeoxythymidylic acid via reverse transcriptase to an extent of 1.0 spin-labeled base per 10(3) bases [20].
• Free radical formation in deoxythymidine-5'-monophosphate gamma-irradiated in frozen solution. A computer-assisted analysis of temperature-dependent ESR spectra [21].
• Incorporation of low concentrations of TdR requires the T4-induced thymidine kinase (tk) and is not significantly affected by the presence or absence of T4-induced thymidylate synthetase (td) [22].

Analytical, diagnostic and therapeutic context of thymidylic acid

• The column has a structure made of two beds-one bed of porous microbeads and one bed of microbeads with a polythymidine base sequence [23].

References