Incorporation of uracil during DNA synthesis is among the most common types of endogenously generated DNA damage. Depletion of Caenorhabditis elegans dUTPase by RNA interference allowed us to study the role of DNA damage response (DDR) pathways when responding to high levels of uracil in DNA. dUTPase depletion compromised development, caused embryonic lethality and led to activation of cell-cyc...

We have previously demonstrated that human cells contain multiple forms of uracil-DNA glycosylase (Caradonna, S. J., Ladner, R., Hansbury, M., Kosciuk, M., Lynch, F., and Muller, S. J. (1996) Exp. Cell Res. 222, 345-359). One of these is an Mr 29,000 processed form of the highly conserved uracil-DNA glycosylase (UDG1) located in the mitochondria. The others are located in the nucleus and migrat...

DNA metabolism and repair is vital for the maintenance of genome integrity. Specific proteinaceous inhibitors of key factors in this process have high potential for deciphering pathways of DNA metabolism and repair. The dUTPase enzyme family is responsible for guarding against erroneous uracil incorporation into DNA. Here, we investigate whether the staphylococcal Stl repressor may interact wit...

[reaction: see text]. A very simple methodology to stereoselectively achieve tricyclic isonucleosides (nucleobase = thymine, uracil, and 5-fluoruracil) and 3'-C-branched nucleosides (nucleobase = theophylline) was performed by means of a DBU-mediated addition process using a readily available 2-bromo sugar. The mechanism for these transformations implies the loss of both substituents at C-2 and...

When Escherichia coli are grown in the presence of 5-fluorouracil, the 5-fluorouracil is incorporated almost exclusively into ribonucleic acid as fluorouridylate. In this study, small but detectable amounts were incorporated into ribonucleic acid as fluorocytidylate and into deoxyribonucleic acid as fluorodeoxyuridylate and fluorodeoxycytidylate. The amount of 5-fluorouracil found in deoxyribon...

Recent multi-photon ionization (MPI) experiments on uracil revealed a fragment ion at m/z 84 that was proposed as a potential marker for ring opening in the electronically excited neutral molecule. The present MPI measurements on deuterated uracil identify the fragment as C3H4N2O (uracil less CO), a plausible dissociative ionization product from the theoretically predicted open-ring isomer. Equ...

In Experiment 1, groups of thirty 6-wk-old male and female F344 rats were given diets containing 0 (control) or 3% uracil for 104 wk. In the uracil-treated groups, carcinomas, in particular transitional cell carcinomas, developed in the urinary bladder of 90% of the males and 19% of the females. Squamous cell carcinomas also developed in 10% of the males, but not in females. Striking findings w...

0.4 Background and Motivation In living organism’s uracil DNA glycosylases (UDG) are used to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosylic bond (Krokan et al., 2002). Uracil can be found in DNA due to misincorporation of dUMP residues or cytosine deamination (Lindahl, 1993). UDG is used in uracil-excision based cloning invented in the beginning of the...

Mutations in mitochondrial DNA (mtDNA) have been reported in cancer and are involved in the pathogenesis of many mitochondrial diseases. Uracil-DNA glycosylase, encoded by the UNG1 gene in Saccharomyces cerevisiae, repairs uracil in DNA formed due to deamination of cytosine. Our study demonstrates that inactivation of the UNG1 gene leads to at least a 3-fold increased frequency of mutations in ...