A novel activity of E. coli uracil DNA N-glycosylase excision of isodialuric acid (5,6-dihydroxyuracil), a major product of oxidative DNA damage, from DNA

• Published in: FEBS letters 1995-05, Vol.364 (3), p.255-258
• Main Authors: Zastawny, Tomasz H., Doetsch, Paul W., Dizdaroglu, Miral
• Format: Article
• Language: English
• Subjects: 2-OH-Ade, 2-hydroxyadenine; 5,6- diHUra, 5,6-dihydrouracil; 5,6-diHThy, 5,6-dihydrothymine; 5,6-diOH-Ura, 5,6-dihydroxyuracil (isodialuric acid); 5-OH-5-MeHyd, 5-hydroxy-5-methylhydantoin; 5-OH-6-HThy, 5-hydroxy-6-hydrothymine; 5-OH-6-HUra, 5-hydroxy-6-hydrouracil; 5-OH-Cyt, 5-hydroxycytosine; 5-OH-Hyd, 5-hydroxyhydantoin; 5-OH-Ura, 5-hydroxyuracil; 5-OHMeUra, 5-(hydroxymethyl)uracil; 8-OH- Gua, 8-hydroxyguanine; 8-OH-Ade, 8-hydroxyadenine; Cytosine - metabolism; DNA - metabolism; DNA - radiation effects; DNA Damage; DNA Glycosylases; DNA repair; Escherichia coli - enzymology; FapyAde, 4,6-diamino-5-for-mamidopyrimidine; FapyGua, 2,6-diamino-4-hydroxy-5-formamidopyrimidine; Free Radicals; Gamma Rays; GC/MS-SIM, gas chromatography-mass spectrometry with selected-ion monitoring; Hydroxyl radical; Isodialuric acid; Kinetics; Modified base; N-Glycosyl Hydrolases - metabolism; OH, hydroxyl radical; Oxidation-Reduction; Oxidative DNA damage; Substrate Specificity; Thy glycol, thymine glycol; U, unit; UNG, uracil DNA N-glycosylase; Uracil - analogs & derivatives; Uracil - metabolism; Uracil-DNA Glycosidase
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(95)00400-4

We describe a novel activity of E. coli uracil DNA N-glycosylase (UNG) that excises isodialuric acid from DNA. Isodialuric acid is formed in DNA as a major oxidative product of cytosine. DNA substrates, which were prepared by γ-irradiation, were incubated with UNG. Following precipitation of DNA, analyses of pellets and supernatant fractions by gas chromatography/mass spectrometry showed an efficient excision of isodialuric acid from DNA by UNG. None of the other 15 identified DNA base lesions was excised. The excision of isodialuric acid indicates that the non-aromaticity of a substrate may not be a limiting factor for UNG.