Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication

Mol Cell. 2000 Jun;5(6):1059-65. doi: 10.1016/s1097-2765(00)80271-3.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / enzymology
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Cytosine / metabolism
  • DNA / biosynthesis
  • DNA / genetics
  • DNA / metabolism
  • DNA Glycosylases*
  • DNA Repair / genetics
  • DNA Replication*
  • Deoxyuracil Nucleotides / metabolism
  • Female
  • Gene Deletion
  • Kinetics
  • Male
  • Mice
  • Mice, Knockout
  • Mutagenesis / genetics
  • N-Glycosyl Hydrolases / deficiency
  • N-Glycosyl Hydrolases / genetics
  • N-Glycosyl Hydrolases / metabolism*
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Uracil / metabolism
  • Uracil-DNA Glycosidase


  • Deoxyuracil Nucleotides
  • Nuclear Proteins
  • Uracil
  • Cytosine
  • DNA
  • 2'-deoxyuridylic acid
  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • Uracil-DNA Glycosidase