1991
DOI: 10.1128/jb.173.21.6807-6810.1991
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The spectrum of spontaneous mutations in a Saccharomyces cerevisiae uracil-DNA-glycosylase mutant limits the function of this enzyme to cytosine deamination repair

Abstract: Uracil-DNA-glycosylase has been proposed to function as the first enzyme in strand-directed mismatch repair in eukaryotic organisms, through removal of uracil from dUMP residues periodically inserted into the DNA during DNA replication (Aprelikova, 0. N., V. M. Golubovskaya, T. A. Kusmin, and N. V. Tomilin, Mutat. Res. 213:135-140, 1989). This hypothesis was investigated with Saccharomyces cerevisiae. Mutation frequencies and spectra were determined for an ungi deletion strain in the target SUP4-o tRNA gene b… Show more

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Cited by 92 publications
(56 citation statements)
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“…The greatly increased frequency of mutations in Saccharomyces cerevisiae ungϪ mutants deficient in UNG demonstrates the importance of this DNA uracil glycosylase (43). Surprisingly, UNG-deficient mice lack the mutator genotype characteristic of bacterial and yeast ungϪ/Ϫ mutations (42), suggesting the existence of complementary uracil-DNA glycosylase activity. Similarly, deficiency in oxoguanine-DNA glycosylase (OGG1), which recognizes and removes 8-oxoguanine, is also not exhibited through an overt phenotype (44).…”
Section: Discussionmentioning
confidence: 99%
“…The greatly increased frequency of mutations in Saccharomyces cerevisiae ungϪ mutants deficient in UNG demonstrates the importance of this DNA uracil glycosylase (43). Surprisingly, UNG-deficient mice lack the mutator genotype characteristic of bacterial and yeast ungϪ/Ϫ mutations (42), suggesting the existence of complementary uracil-DNA glycosylase activity. Similarly, deficiency in oxoguanine-DNA glycosylase (OGG1), which recognizes and removes 8-oxoguanine, is also not exhibited through an overt phenotype (44).…”
Section: Discussionmentioning
confidence: 99%
“…Another possible source of uracil in DNA is the enzymic deamination of cytosine by (cytosine-5)-methyltransferase under certain conditions [23]. E. coli and yeast mutants in UDG have, depending on the sequence context, 4-30-fold increases in G :C A:T transition mutations [24,25]. It is believed that the primary function of UDG is to remove uracil from U\G mispairs resulting from the deamination of cytosine [1,25].…”
Section: Udgsmentioning
confidence: 99%
“…E. coli and yeast mutants in UDG have, depending on the sequence context, 4-30-fold increases in G :C A:T transition mutations [24,25]. It is believed that the primary function of UDG is to remove uracil from U\G mispairs resulting from the deamination of cytosine [1,25].…”
Section: Udgsmentioning
confidence: 99%
“…It has been hypothesized that incorporated dUMP, or strand breaks resulting from repair of newly replicated DNA, may have a role in strand selection in mismatch repair (reviewed in [6]), but to our knowledge there is no direct experimental evidence supporting this view. E. coli mutants in the ung-gene encoding uracil-DNA glycosylase show some 5-fold increased spontaneous mutation rate [7] rising to 30-fold at certain bases [8], whereas a 20-fold increase in spontaneous mutations has been found in similar yeast mutants [9]. Mammalian mutants in the UNG-gene are not available.…”
Section: Introductionmentioning
confidence: 99%