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

[摘要]

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.

[学科分类] 生物化学/生物物理

[关键词] Oxidative DNA damage;Hydroxyl radical;DNA repair;Modified base;Isodialuric acid;UNG;uracil DNA N-glycosylase;OH;hydroxyl radical;GC/MS-SIM;gas chromatography-mass spectrometry with selected-ion monitoring;U;unit;5-OH-5-MeHyd;5-hydroxy-5-methylhydantoin;5-OH-Hyd;5-hydroxyhydantoin;5-OHMeUra;5-(hydroxymethyl)uracil;5-OH-Ura;5-hydroxyuracil;5-OH-Cyt;5-hydroxycytosine;Thy glycol;thymine glycol;5;6-diOH-Ura;5;6-dihydroxyuracil (isodialuric acid);FapyAde;4;6-diamino-5-for-mamidopyrimidine;8-OH-Ade;8-hydroxyadenine;2-OH-Ade;2-hydroxyadenine;FapyGua;2;6-diamino-4-hydroxy-5-formamidopyrimidine;8-OH- Gua;8-hydroxyguanine;5;6-diHThy;5;6-dihydrothymine;5;6- diHUra;5;6-dihydrouracil;5-OH-6-HThy;5-hydroxy-6-hydrothymine;5-OH-6-HUra;5-hydroxy-6-hydrouracil