Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication.
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.
Imperial Cancer Research Fund, Clare Hall Laboratories, Hertfordshire, United Kingdom.
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H
Nilsen
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I
Rosewell
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P
Robins
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CF
Skjelbred
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Andersen
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Slupphaug
G
G
Daly
H E
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Krokan
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Lindahl
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Barnes
D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003596:Cytosine / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D045647:DNA Glycosylases; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication; D003856:Deoxyuracil Nucleotides / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D007700:Kinetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016296:Mutagenesis / Q000235:genetics; D009699:N-Glycosyl Hydrolases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014498:Uracil / Q000378:metabolism; D051981:Uracil-DNA Glycosidase
D003856:Deoxyuracil Nucleotides; D009687:Nuclear Proteins; D014498:Uracil; D003596:Cytosine; D004247:DNA; C007267:2'-deoxyuridylic acid; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase