DNA sequences determined from ancient organisms have high error rates, primarily due to uracil bases created by cytosine deamination. We use synthetic oligonucleotides, as well as DNA extracted from mammoth and Neandertal remains, to show that treatment with uracil-DNA-glycosylase and endonuclease VIII removes uracil residues from ancient DNA and repairs most of the resulting abasic sites, leav...

Radiolysis products resulting from the deamination pathway were isolated and identified after irradiation of cytosine by gamma rays in neutral aqueous solutions. They were identical to those identified in uracil radiolysis i. e. 5,6-dihydroxy-5,6-dihydro-uracil (cis and trans forms), iso-dialuric acid, alloxan, 5-hydroxy-hydantoin, parabanic acid and oxaluric acid. The absence of 4,4'-di-iso-ba...

The metabolism of exogenous uridine, uridine 5’-monophosphate, and uracil by rat liver slices was studied using in vitro superfusion systems. Mixtures of 3Hand 14Clabeled uridine, uridine 5’-monophosphate, uracil, and erotic acid were superfused at a constant rate until an isotopic steady state was achieved. Isotopic ratios and concentrations of labeled pyrimidines were measured in tissue and p...

No genes for any of the known uracil DNA glycosylases of the UDG superfamily are present in the genome of Methanothermobacter thermautotrophicus DeltaH, making it difficult to imagine how DNA-U repair might be initiated in this organism. Recently, Mth212, the ExoIII homologue of M. thermautotrophicus DeltaH has been characterized as a DNA uridine endonuclease, which suggested the possibility of...

The excited state properties of uracil, thymine and four analogous uracil compounds have been studied in acetonitrile by steady-state and time-resolved spectroscopy. The excited state lifetimes were measured using femtosecond UV fluorescence upconversion. The excited state lifetimes of uracil and its 1and 3-methyl substituted derivatives are well described by one ultrafast (6100 fs) component. ...

The stereoselective synthesis of some 3’-deoxy-3’-C-methyl pyrimidine nucleosides is reported. studied modifications concern the inversion configuration in 2’-position as well introduction fluoro and azido substituents. corresponding arabinonucleoside 2’-substituted ribonucleoside analogs uracil cytosine have been obtained fully characterized. Attempts to introduce substituents with at C-2’ are...

Activation-induced deaminase (AID) catalyses deamination of deoxycytidine to deoxyuridine within immunoglobulin loci, triggering pathways of antibody diversification that are largely dependent on uracil-DNA glycosylase (uracil-N-glycolase [UNG]). Surprisingly efficient class switch recombination is restored to ung(-/-) B cells through retroviral delivery of active-site mutants of UNG, stimulati...

The thymidylate synthase reaction remains an important target for widely used anticancer agents; however, the clinical utility of these drugs is limited by the occurrence of cellular resistance. Despite the considerable amount of information available regarding mechanisms of drug action, the relative significance of downstream events that result in lethality remains unclear. In this study, we h...