Base excision repair (BER) is initiated by a DNA glycosylase and is completed by alternative routes, one of which requires proliferating cell nuclear antigen (PCNA) and other proteins also involved in DNA replication. We report that the major nuclear uracil-DNA glycosylase (UNG2) increases in S phase, during which it co-localizes with incorporated BrdUrd in replication foci. Uracil is rapidly r...

Recent investigations have shown that the animal microorganism, Tetrahymena geleii, requires an exogenous source of pyrimidine for growth (1). This requirement can be met by the addition of cytidylic acid or uracil to the medium (2). Cytosine and thymine are without activity. The failure to utilize the latter two free bases was interpreted as indicating a block in the ability of the organism to...

A uracil-DNA-glycosylase from Micrococcus luteus has been purified more than 3,000-fold. The enzyme preparation appears homogeneous, according to the results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It is devoid of nonspecific endonucleases, specific endonucleases for apurinic and apyrimidinic sites, 3-methyladenine or 7-methylguanine-DNA-glycosylases. It behaves as a monom...

Dihydropyrimidine dehydrogenase (DPD), the first enzyme in the sequential metabolism of pyrimidine, regulates blood concentrations of 5-fluorouracil and is deeply involved in its toxicity. This study was designed to examine the effects of a DPD inhibitor on blood concentrations of [2-(13)C]uracil ([(13)C]uracil) and (13)CO(2) concentration (Delta(13)C) expired in breath after oral or intravenou...

The role of the conserved histidine-187 located in the leucine intercalation loop of Escherichia coli uracil-DNA glycosylase (Ung) was investigated. Using site-directed mutagenesis, an Ung H187D mutant protein was created, overproduced, purified to apparent homogeneity, and characterized in comparison to wild-type Ung. The properties of Ung H187D differed from Ung with respect to specific activ...

The pyrimidine-deficient mutant (1298) of Neurospora crassa, utilizes erotic acid, uracil, uridine, or cytidine for growth, but neither cytosine nor thymine (1). It seems likely, therefore, that this mutant can convert erotic acid and uracil to the pyrimidine bases of ribonucleic acid and deoxyribonucleic acid, and can utilize the nucleoside directly for ribonucleic acid biosynthesis and for co...

It has been shown that uracil can be incorporated into ribonucleic acid of the normal rat tissues (2). However, this incorporation becomes significant only when the enzymes associated with the catabolism of uracil are saturated with their substrates. When thii is achieved, the incorporation of uracil into RNA increases with substrate concentration. At high concentrations the extent of incorpora...