Although the combination of uracil and tegafur (UFT) has been available commercially in Japan since 1984 and is one of the most extensively prescribed antineoplastic agents in that country, few physicians outside Japan have knowledge of and experience with the drug. The development of UFT, which combines uracil and tegafur in a 4:1 molar concentration, dates back to the pioneering work of Fujii...

Most of the literature dealing with the participation of citrovorum factor and vitamin Blz in the formation and transfer of l-carbon intermediates stresses the donor compounds serine, glycine, and formate as precursors of the 5-methyl group of thymidine (2). Uracil deoxyriboside, first isolated in crystalline form by Dekker and Todd (3) in 1950, is known to arise as a result of the deamination ...

We present the experimental results from ionization and dissociation by multiphoton absorption (MPI) of uracil and a mixture of uracil with Ar using a Reflectron time of flight spectrometer along with radiation from 355 nm at pulsed Nd:YAG laser . We focus on the light ions production. The MPI mass spectra show that the presence and intensity of the resulting ions depend on the density power of...

The Histoplasma capsulatum URA5 gene, which has recently been cloned and disrupted by allelic replacement, encodes orotidine-5'-monophosphate pyrophosphorylase. Inactivation of URA5 by either targeted or UV mutagenesis results in disruption of the pyrimidine biosynthetic pathway and uracil auxotrophy. We examined the effect of uracil auxotrophy due to a ura5 mutation on H. capsulatum virulence ...

A first derivative spectrometric method has been developed for the determination of the 5-fluorouracil and N1(2'-furanidyl)uracil related substances and degradation products of tegafur. The wavelengths selected for the determination of 5-fluorouracil and N1(2'-furanidyl)uracil were 298 and 288 nm, respectively. At this wavelength, the calibration graphs between the amplitude of the signals and ...

We demonstrate that a mutant of uracil DNA glycosylase (N123D:L191A) distinguishes between cytosine and methylcytosine. Uracil DNA glycosylase (UDG) efficiently removes uracil from DNA in a reaction in which the base is flipped into the enzyme's active site. Uracil is selected over cytosine by a pattern of specific hydrogen bonds, and thymine is excluded by steric clash of its 5-methyl group wi...

Uracil DNA glycosylase (UDG), a highly conserved DNA repair enzyme, excises uracil from DNA. Crystal structures of several UDGs have identified residues important for their exquisite specificity in detection and removal of uracil. Of these, Y66 and N123 in Escherichia coli UDG have been proposed to restrict the entry of non-uracil residues into the active site pocket. In this study, we show tha...

Uracil residues arise in DNA by the misincorporation of dUMP in place of dTMP during DNA replication or by the deamination of cytosine in DNA. Uracil-DNA glycosylase initiates DNA base excision repair of uracil residues by catalyzing the hydrolysis of the N-glycosylic bond linking the uracil base to deoxyribose. In human cells, the nuclear form of uracil-DNA glycosylase (UNG2) contains a conser...

Uracil DNA glycosylase (UNG) is the primary enzyme for the removal of uracil from the genome of many organisms. A key question is how the enzyme is able to scan large quantities of DNA in search of aberrant uracil residues. Central to this is the mechanism by which it flips the target nucleotide out of the DNA helix and into the enzyme-active site. Both active and passive mechanisms have been p...

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. This DNA glycosylase presumably functions to eliminate hydroxymethyluracil, a major thymine-derived DNA lesion produced by ionizing radiation and oxidative damage. The en...