Abstract
Gene-targeted knockout mice have been generated lacking the major uracil-DNA glycosylase, UNG. In contrast to ung- mutants of bacteria and yeast, such mice do not exhibit a greatly increased spontaneous mutation frequency. However, there is only slow removal of uracil from misincorporated dUMP in isolated ung-/- nuclei and an elevated steady-state level of uracil in DNA in dividing ung-/- cells. A backup uracil-excising activity in tissue extracts from ung null mice, with properties indistinguishable from the mammalian SMUG1 DNA glycosylase, may account for the repair of premutagenic U:G mispairs resulting from cytosine deamination in vivo. The nuclear UNG protein has apparently evolved a specialized role in mammalian cells counteracting U:A base pairs formed by use of dUTP during DNA synthesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Nucleus / enzymology
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Cell Nucleus / genetics
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Cell Nucleus / metabolism
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Cells, Cultured
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Cytosine / metabolism
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DNA / biosynthesis
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DNA / genetics
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DNA / metabolism
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DNA Glycosylases*
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DNA Repair / genetics
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DNA Replication*
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Deoxyuracil Nucleotides / metabolism
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Female
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Gene Deletion
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Kinetics
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Male
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Mice
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Mice, Knockout
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Mutagenesis / genetics
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N-Glycosyl Hydrolases / deficiency
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N-Glycosyl Hydrolases / genetics
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N-Glycosyl Hydrolases / metabolism*
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Nuclear Proteins / deficiency
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Uracil / metabolism
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Uracil-DNA Glycosidase
Substances
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Deoxyuracil Nucleotides
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Nuclear Proteins
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Uracil
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Cytosine
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DNA
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2'-deoxyuridylic acid
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DNA Glycosylases
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N-Glycosyl Hydrolases
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Uracil-DNA Glycosidase