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Gene Review

ung  -  uracil-DNA glycosylase

Escherichia coli O157:H7 str. EDL933

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Disease relevance of ung

  • Quantitative determination of uracil residues in Escherichia coli DNA: Contribution of ung, dug, and dut genes to uracil avoidance [1].
  • T5 phage containing 12% uracil can replicate in uracil-DNA glycosylase-deficient (ung) hosts with high efficiency, but fail to replicate in ung+ hosts [2].
  • Wild-type cells were more sensitive to BrdU photosensitization than ung mutant cells [3].
  • Human glioblastoma U251 and colon adenocarcinoma LoVo whole-cell extracts repaired the uracil residue to produce form I DNA that was resistant to subsequent in vitro cleavage by E. coli uracil-DNA glycosylase (Ung) and endonuclease IV, indicating that complete uracil-initiated BER repair had occurred [4].
  • To determine whether this mechanism could contribute to the development of human colon cancer, we examined the level of DNA (cytosine-5)-methyltransferase (MTase) expression, the concentration of AdoMet, and the activity of uracil-DNA glycosylase in human colon tissues, and searched for the presence of mutations in the MTase gene [5].

High impact information on ung

  • Uracil is removed in a base-excision repair pathway by uracil DNA-glycosylase (UDG), which excises uracil from both single- and double-stranded DNA [6].
  • These data imply the existence of a family of double-strand-specific uracil-DNA glycosylases which, although they are subservient to UDG in most organisms, may constitute the first line of defence against the mutagenic effects of cytosine deamination in insects [7].
  • Pupating insects have been reported to lack UDG activity, but we have identified an enzyme similar to dsUDG in cell lines from three different insect species [7].
  • We show here that in bacteria which lack uracil-DNA glycosylase (Ung-) and cannot excise uracil residues from DNA, the rate of spontaneous transition at cytosine residues is raised to the hotspot rate at 5-methylcytosine residues [8].
  • A novel uracil-DNA glycosylase with broad substrate specificity and an unusual active site [9].

Chemical compound and disease context of ung


Biological context of ung

  • In contrast, the ung and mutY mutants did not show higher frequencies of intergenomic recombination or greater sensitivity to UV-induced DNA damage than the wild type [14].
  • Exposure of a test double-stranded plasmid containing C or 5mC at the target site to NO in phosphate-buffered solution at pH 7.4 followed by transformation into Escherichia coli ung- strain to avoid repair of U did not result in a significant increase in reversion frequency [15].
  • Recombination was very low in ung cells, suggesting that excision repair was responsible for the stimulation [16].
  • The ung gene maps between tyrA and nadB on the E. coli chromosome [17].
  • These physiological properties are consistent with the phenotypes of other ung mutants [18].

Anatomical context of ung

  • We have purified uracil DNA-glycosylase (UDG) from calf thymus 32,000-fold and studied its biochemical properties, including sequence specificity [19].
  • Infection of cultured mammalian cells with the Leporipoxvirus Shope fibroma virus (SFV) causes the induction of a novel uracil DNA glycosylase activity in the cytoplasms of the infected cells [20].
  • Another species of uracil-DNA glycosylase has been partially purified from mitochondria [21].
  • Furthermore, > 98% of the total uracil-DNA glycosylase activity from HeLa cell extracts was inhibited by the antibodies, indicating that the UNG protein represents the major uracil-DNA glycosylase in the cells [22].
  • A nuclear and a cytoplasmic uracil-DNA glycosylase have been purified from epithelial cells derived from a rat hepatoma (H4 cells) cultured in vitro [23].

Associations of ung with chemical compounds

  • Cell-free extracts from mug(+) ung cells show very little ability to remove uracil from DNA, but can excise epsilonC [11].
  • Since the ung mutation is phenotypically expressed as a defect in uracil DNA glycosidase, this observation supports the contention that treatment of cells with nitrous acid causes deamination of cytosine to uracil [24].
  • The ability of the wheat germ uracil-DNA glycosylase to completely remove available uracil from synthetic DNA substrates in which thymine had been replaced by uracil in varying percentages was also examined and found not to depend on percentage of uracil in the substrates [25].
  • The DNA repair enzyme uracil DNA glycosylase (UDG) hydrolyzes the glycosidic bond of deoxyuridine in DNA by a remarkable mechanism involving formation of a positively charged oxacarbenium ion-uracil anion intermediate [26].
  • Furthermore, when the Ung.Ugi complex was treated with urea and resolved by urea-polyacrylamide gel electrophoresis, both uracil-DNA glycosylase and inhibitor activities were recovered from the dissociated complex [27].

Other interactions of ung

  • Thermal resistance to photoreactivation of ultraviolet light induced mutations in the lacI gene of E. coli ung [28].
  • Escherichia coli mutants defective in DNA uracil N-glycosidase (ung-) or endonuclease VI active against apurinic/apyrimidinic sites in DNA (xthA-) exhibit enhanced sensitivity towards 5-bromodeoxyuridine relative to the wild type strain, pointing to involvement of these enzymes in repair of bromouracil-induced lesions in DNA [29].

Analytical, diagnostic and therapeutic context of ung

  • Neutral agarose gel electrophoresis of minipreps indicated that UV induced (1) more smears of host BrU-DNA possibly by more double-strand breaks (DSB) and (2) a greater decline of pBR322 Form I BrU-DNA in the wild-type cells than the ung cells [3].
  • Molecular cloning and primary structure of the uracil-DNA-glycosylase gene from Saccharomyces cerevisiae [30].
  • Crystallization and preliminary X-ray analysis of the uracil-DNA glycosylase DNA repair enzyme from herpes simplex virus type 1 [31].
  • These observations are generally not apparent from the high-resolution crystal structures of UDG and its complexes with DNA; thus, Raman spectroscopy can provide unique and valuable insights into the nature of enzyme-DNA interactions [32].
  • In the following paper of this issue we establish by crystallography and heteronuclear NMR spectroscopy that the imidazole of His187 is neutral during the catalytic cycle of UDG [33].


  1. Quantitative determination of uracil residues in Escherichia coli DNA: Contribution of ung, dug, and dut genes to uracil avoidance. Lari, S.U., Chen, C.Y., Vert??ssy, B.G., Morr??, J., Bennett, S.E. DNA Repair (Amst.) (2006) [Pubmed]
  2. The properties of a bacteriophage T5 mutant unable to induce deoxyuridine 5'-triphosphate nucleotidohydrolase. Synthesis of uracil-containing T5 deoxyribonucleic acid. Warner, H.R., Thompson, R.B., Mozer, T.J., Duncan, B.K. J. Biol. Chem. (1979) [Pubmed]
  3. Roles of uracil-DNA glycosylase and apyrimidinic endonucleases in the molecular 5-bromo-2'-deoxyuridine photosensitization in Escherichia coli K-12. Yamamoto, Y., Fujiwara, Y. Photochem. Photobiol. (1993) [Pubmed]
  4. Uracil-initiated base excision DNA repair synthesis fidelity in human colon adenocarcinoma LoVo and Escherichia coli cell extracts. Sanderson, R.J., Bennett, S.E., Sung, J.S., Mosbaugh, D.W. Prog. Nucleic Acid Res. Mol. Biol. (2001) [Pubmed]
  5. Mechanisms for the involvement of DNA methylation in colon carcinogenesis. Schmutte, C., Yang, A.S., Nguyen, T.T., Beart, R.W., Jones, P.A. Cancer Res. (1996) [Pubmed]
  6. Crystal structure of a G:T/U mismatch-specific DNA glycosylase: mismatch recognition by complementary-strand interactions. Barrett, T.E., Savva, R., Panayotou, G., Barlow, T., Brown, T., Jiricny, J., Pearl, L.H. Cell (1998) [Pubmed]
  7. A new class of uracil-DNA glycosylases related to human thymine-DNA glycosylase. Gallinari, P., Jiricny, J. Nature (1996) [Pubmed]
  8. Mutagenic deamination of cytosine residues in DNA. Duncan, B.K., Miller, J.H. Nature (1980) [Pubmed]
  9. A novel uracil-DNA glycosylase with broad substrate specificity and an unusual active site. Sartori, A.A., Fitz-Gibbon, S., Yang, H., Miller, J.H., Jiricny, J. EMBO J. (2002) [Pubmed]
  10. The structure of cruciforms in supercoiled DNA: probing the single-stranded character of nucleotide bases with bisulphite. Gough, G.W., Sullivan, K.M., Lilley, D.M. EMBO J. (1986) [Pubmed]
  11. The role of the Escherichia coli mug protein in the removal of uracil and 3,N(4)-ethenocytosine from DNA. Lutsenko, E., Bhagwat, A.S. J. Biol. Chem. (1999) [Pubmed]
  12. Characterization of the uracil-DNA glycosylase activity of Epstein-Barr virus BKRF3 and its role in lytic viral DNA replication. Lu, C.C., Huang, H.T., Wang, J.T., Slupphaug, G., Li, T.K., Wu, M.C., Chen, Y.C., Lee, C.P., Chen, M.R. J. Virol. (2007) [Pubmed]
  13. The cloning and overproduction of Escherichia coli uracil-DNA glycosylase. Duncan, B.K., Chambers, J.A. Gene (1984) [Pubmed]
  14. Antimutator role of the DNA glycosylase mutY gene in Helicobacter pylori. Huang, S., Kang, J., Blaser, M.J. J. Bacteriol. (2006) [Pubmed]
  15. Mutagenicity of nitric oxide is not caused by deamination of cytosine or 5-methylcytosine in double-stranded DNA. Schmutte, C., Rideout, W.M., Shen, J.C., Jones, P.A. Carcinogenesis (1994) [Pubmed]
  16. Recombination of uracil-containing lambda bacteriophages. Hays, J.B., Duncan, B.K., Boehmer, S. J. Bacteriol. (1981) [Pubmed]
  17. Escherichia coli K-12 mutants deficient in uracil-DNA glycosylase. Duncan, B.K., Rockstroh, P.A., Warner, H.R. J. Bacteriol. (1978) [Pubmed]
  18. Uracil-DNA glycosylase inhibitor of bacteriophage PBS2: cloning and effects of expression of the inhibitor gene in Escherichia coli. Wang, Z., Mosbaugh, D.W. J. Bacteriol. (1988) [Pubmed]
  19. Consensus sequences for good and poor removal of uracil from double stranded DNA by uracil-DNA glycosylase. Eftedal, I., Guddal, P.H., Slupphaug, G., Volden, G., Krokan, H.E. Nucleic Acids Res. (1993) [Pubmed]
  20. A poxvirus-encoded uracil DNA glycosylase is essential for virus viability. Stuart, D.T., Upton, C., Higman, M.A., Niles, E.G., McFadden, G. J. Virol. (1993) [Pubmed]
  21. Purification of nuclear and mitochondrial uracil-DNA glycosylase from rat liver. Identification of two distinct subcellular forms. Domena, J.D., Mosbaugh, D.W. Biochemistry (1985) [Pubmed]
  22. Properties of a recombinant human uracil-DNA glycosylase from the UNG gene and evidence that UNG encodes the major uracil-DNA glycosylase. Slupphaug, G., Eftedal, I., Kavli, B., Bharati, S., Helle, N.M., Haug, T., Levine, D.W., Krokan, H.E. Biochemistry (1995) [Pubmed]
  23. Comparison at the molecular level of uracil-DNA glycosylases from different origins. Leblanc, J.P., Laval, J. Biochimie (1982) [Pubmed]
  24. Repair of nitrous acid damage to DNA in Escherichia coli. Da Roza, R., Friedberg, E.C., Duncan, B.K., Warner, H.R. Biochemistry (1977) [Pubmed]
  25. Partial purification and characterization of a uracil-DNA glycosylase from wheat germ. Blaisdell, P., Warner, H. J. Biol. Chem. (1983) [Pubmed]
  26. Probing the limits of electrostatic catalysis by uracil DNA glycosylase using transition state mimicry and mutagenesis. Jiang, Y.L., Drohat, A.C., Ichikawa, Y., Stivers, J.T. J. Biol. Chem. (2002) [Pubmed]
  27. Characterization of the Escherichia coli uracil-DNA glycosylase.inhibitor protein complex. Bennett, S.E., Mosbaugh, D.W. J. Biol. Chem. (1992) [Pubmed]
  28. Thermal resistance to photoreactivation of ultraviolet light induced mutations in the lacI gene of E. coli ung. Fix, D.F., Glickman, B.W. Mutat. Res. (1987) [Pubmed]
  29. Genetic evidence for the nature, and excision repair, of DNA lesions resulting from incorporation of 5-bromouracil. Krych, M., Pietrzykowska, I., Szyszko, J., Shugar, D. Mol. Gen. Genet. (1979) [Pubmed]
  30. Molecular cloning and primary structure of the uracil-DNA-glycosylase gene from Saccharomyces cerevisiae. Percival, K.J., Klein, M.B., Burgers, P.M. J. Biol. Chem. (1989) [Pubmed]
  31. Crystallization and preliminary X-ray analysis of the uracil-DNA glycosylase DNA repair enzyme from herpes simplex virus type 1. Savva, R., Pearl, L.H. J. Mol. Biol. (1993) [Pubmed]
  32. Raman spectroscopy of uracil DNA glycosylase-DNA complexes: insights into DNA damage recognition and catalysis. Dong, J., Drohat, A.C., Stivers, J.T., Pankiewicz, K.W., Carey, P.R. Biochemistry (2000) [Pubmed]
  33. Role of electrophilic and general base catalysis in the mechanism of Escherichia coli uracil DNA glycosylase. Drohat, A.C., Jagadeesh, J., Ferguson, E., Stivers, J.T. Biochemistry (1999) [Pubmed]
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