Disease relevance of 5-Oxymethyluracil

• The Bacillus subtilis phage SP01, whose DNA contains 5-hydroxymethyluracil (hmUra) in place of thymine, codes for an abundant, small, basic protein called TF1 [1].
• An activity has been purified 350-fold from extracts of mouse plasmacytoma cells that forms 5-hydroxymethyluracil (alpha-hydroxythymine) and apyrimidinic sites with phage SPO1 DNA, which contains this base in place of thymine [2].
• Effects of 5-hydroxymethyluracil and 3-aminobenzamide on the repair and toxicity of 5-hydroxymethyl-2'-deoxyuridine in mammalian cells [3].
• DNA binding by the bacteriophage SPO1-encoded type II DNA-binding protein, transcription factor 1. Site-specific binding requires 5-hydroxymethyluracil-containing DNA [4].
• We have investigated the binding of TF1 to one of its preferred sites in which the normal 5-hydroxymethyluracil (hmUra) of SPO1 DNA has been replaced by thymine and have also investigated the binding of a bacterial Type II DNA-binding protein (from Bacillus stearothermophilus) to the hmUra- and thymine-containing forms of the same DNA segment [4].

High impact information on 5-Oxymethyluracil

• The levels of oxidized thymine, specifically 5-hydroxymethyluracil, were threefold higher in the nonintervention diet group than in the low-fat diet group [5].
• Both promoters shared the identical hexanucleotide 5'A-G-G-A-G-A at about 35 base pairs preceding the start point of transcription and the identical heptanucleotide 5'-T-T-T-A-T-T-T (T is the thymine analog 5-hydroxymethyluracil in SP01 DNA) located about 10 base pairs preceding the transcriptional start point [6].
• Definitive identification of mammalian 5-hydroxymethyluracil DNA N-glycosylase activity as SMUG1 [7].
• Since both 5-formyluracil and 5-hydroxymethyluracil are major products formed in DNA by exposure to ionizing radiation, these results implicate the alkA gene function also in the repair of oxidative DNA damage [8].
• The essentially homogeneous preparations of the 7-hydroxylase were shown to catalyze the thymine-, 5-hydroxymethyluracil-, and 5-formyluracil-dependent oxygenations that are coupled to the decarboxylation of alpha-ketoglutarate, as well as a putative uncoupled decarboxylation which is dependent on uracil [9].

Chemical compound and disease context of 5-Oxymethyluracil

• Toxicity of 3-aminobenzamide to Chinese hamster cells containing 5-hydroxymethyluracil in their DNA [10].
• Identification of high excision capacity for 5-hydroxymethyluracil mispaired with guanine in DNA of Escherichia coli MutM, Nei and Nth DNA glycosylases [11].

Biological context of 5-Oxymethyluracil

• Distinctive to TF1, which is encoded by the Bacillus subtilis bacteriophage SPO1, is its preferential binding to DNA in which thymine is replaced by 5-hydroxymethyluracil (hmU), as it is in the phage genome [12].
• However, hmdUrd did not induce apoptosis in V79mut1 cells, which are deficient in DNA base excision repair of 5-hydroxymethyluracil (hmUra) [13].
• The degradation of 5-(hydroxymethyl)uracil was avoided using enzymatic hydrolysis of the DNA [14].
• Characterization of the substrate specificity of a human 5-hydroxymethyluracil glycosylase activity [15].
• These findings support the hypotheses that 5-hydroxymethyluracil (HmUra) residues in DNA are formed and then removed by the action of 5-HmUra-DNA glycosylase (Teeber et al., 1984) and that 3AB interferes with the completion of DNA repair following HmUra excision [16].

Anatomical context of 5-Oxymethyluracil

• Purification from calf thymus of a DNA N-glycosylase activity (HMUDG) that released 5-hydroxymethyluracil (5hmUra) from the DNA of Bacillus subtilis phage SPO1 was undertaken [7].
• 5-(Hydroxymethyl)uracil (HMUra) is a chemically stable derivative of thymine formed through the action of ionizing radiation which we previously identified in the DNA of gamma-irradiated HeLa cells [Teebor, G. W., Frenkel, K., & Goldstein, M. S. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 318-321] [17].
• We have examined the effects of changes in dietary fat and caloric intake on the levels of 5-hydroxymethyluracil in DNA from rat liver and mammary gland [18].

Associations of 5-Oxymethyluracil with other chemical compounds

• Emphasis was placed in this work on the measurement of four oxidized pyrimidine bases, including 5-(hydroxymethyl)uracil (5-HMUra), 5-formyluracil (5-ForUra), 5-hydroxycytosine (5-OHCyt), and 5-hydroxyuracil (5-OHUra), in isolated DNA upon exposure to gamma radiation in aerated aqueous solution [19].
• Electrophoric derivatives of 5-methylcytosine and 5-hydroxymethyluracil nucleobases are determined using high-performance liquid chromatography-mass spectrometry coupled via a moving-belt interface [20].
• The method was successfully applied to the detection and the measurement of adenine N1-oxide and 5-hydroxymethyluracil in cells exposed to agents inducing oxidative stress including H2O2 and UV-A radiation [21].

Gene context of 5-Oxymethyluracil

• Furthermore, hNEIL1 efficiently cleaved double stranded oligonucleotides containing 5-formyluracil (5-foU) and 5-hydroxymethyluracil (5-hmU) in vitro via beta- and delta-elimination reactions [22].
• Excessive base excision repair of 5-hydroxymethyluracil from DNA induces apoptosis in Chinese hamster V79 cells containing mutant p53 [13].
• The compound was hydrolyzed to 5-hydroxymethyluracil (5HmUra) by the enzyme thymidine phosphorylase (EC 2.4.2.4) present in leukemia cells; this catabolic product was non-toxic [23].
• In three cases with DHPD deficiency, two were siblings, one with symptoms and the other without, n was 12 for T and 5.9 for U, and 5-hydroxymethyluracil was distinctly detected [24].

Analytical, diagnostic and therapeutic context of 5-Oxymethyluracil

• Quantitation of 5-(hydroxymethyl)uracil in DNA by gas chromatography with mass spectral detection [14].
• Restriction, methylation and ligation of 5-hydroxymethyluracil-containing DNA [25].

References