Letter to the Editor:: Base excision repair:: NMR backbone assignments of Escherichia coli formamidopyrimidine-DNA glycosylase
Letter to the Editor:: Base excision repair:: NMR backbone assignments of Escherichia coli formamidopyrimidine-DNA glycosylase
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DOI：
10.1023/a:1014903518628
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发表时间：
2002-03-01
影响因子：
2.7
通讯作者：
Kennedy, MA
中科院分区：
文献类型：
--
作者：
Buchko, GW;Wallace, SS;Kennedy, MA
氧化损伤正在成为导致突变、癌症、衰老和各种疾病的最重要的机制之一(Farr和Kogma，1991)。氧化的潜在目标之一是细胞DNA。虽然暴露在外部因素，如电离辐射和化学物质，有助于破坏DNA，但最重要的氧化剂是内源性的，例如在正常氧化代谢过程中产生的反应性自由基(Adelman et.，1988)。为了减轻氧化DNA损伤的潜在有害影响，几乎所有需氧生物都发展了复杂的修复机制(Petit和Sancar，1999)。一种修复机制，碱基切除修复(BER)，似乎负责取代大多数氧化DNA损伤(David和Williams，1998)。甲胺嘧啶-DNA糖基酶(FPG)是原核生物中一种关键的BER酶(Boiteaux et al.，1987)，它是一种由269个残基组成的金属蛋白，分子量为30.2 kDa。FPG识别和释放的底物包括7，8-二氢-8-氧鸟嘌呤(8-oxoG)、2，6-二氨基-4-羟基-5-甲酰胺基嘧啶(Fapy-G)、腺嘌呤的等价物8-oxoA和Fapy-A、5-羟基胞嘧啶、5-羟基尿嘧啶、B尿苷异丁酸和a-R-羟基-B-尿苷异丁酸(Freidberg等，1995)。在体外，FPG与双链DNA结合，具有三种催化活性：(I)DNA糖基酶，(Ii)AP裂解酶和(Iii)脱氧核磷二酯酶。
Oxidative damage is emerging as one of the most important mechanisms responsible for mutagenesis, carcinogenesis, aging, and various diseases (Farr and Kogma, 1991). One of the potential targets for oxidation is cellular DNA. While exposure to exogenous agents, such as ionizing radiation and chemicals, contributes to damaging DNA, the most important oxidative agents are endogenous, such as the reactive free radicals produced during normal oxidative metabolism (Adelman et., 1988). To mitigate the potentially deleterious effects of oxidative DNA damage virtually all aerobic organisms have developed complex repair mechanisms (Petit and Sancar, 1999). One repair mechanism, base excision repair (BER), appears to be responsible for replacing most oxidative DNA damage (David and Williams, 1998). Formamidopyrimidine-DNA glycosylase (Fpg), a 269-residue metalloprotein with a molecular weight of 30.2 kDa, is a key BER enzyme in prokaryotes (Boiteaux et al., 1987). Substrates recognized and released by Fpg include 7,8-dihydro-8-oxoguanine (8-oxoG), 2,6 diamino-4-hydroxy-5-formamido pyrimidine (Fapy-G), the adenine equivalents 8-oxoA and Fapy-A, 5-hydroxycytosine, 5-hydroxyuracil, B ureidoisobutiric acid, and a-R-hydroxy-B-ureidoisobutiric acid (Freidberg et al., 1995). In vitro Fpg bind double-stranded DNA and performs three catalytic activities: (i) DNA glycosylase, (ii) AP lyase, and (iii) deoxyribophosphodiesterase.