Oxidative damage to 5-methylcytosine in DNA.

Oxidative damage to 5-methylcytosine in DNA.
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DNA 中 5-甲基胞嘧啶的氧化损伤。

DOI:
10.1093/nar/23.16.3239
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发表时间:
1995
影响因子:
14.9
通讯作者:
Teebor,GW
Teebor,GW
中科院分区:
生物学2区
文献类型:
--
作者:
Zuo,S;Boorstein,RJ;Teebor,GW

文献摘要

被引文献

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DNA的嘧啶在需氧条件下暴露于电离辐射或氧化剂导致嘧啶环的5,6双键或外环5-甲基受到攻击。胸腺嘧啶的5,6双键氧化的主要产物是胸腺嘧啶乙二醇,而5-甲基的氧化产生5-羟甲基尿嘧啶。胞嘧啶的5,6双键氧化产生胞嘧啶二醇,后者分解为5-羟基胞苷、5-羟基尿嘧啶和尿嘧啶二醇,所有这些都在DNA中被大肠杆菌核酸内切酶III修复。我们现在描述DNA中5-甲基胞嘧啶的氧化产物。聚(dG-[3 H]dmC)在Fe ~(3+)和抗坏血酸存在下,经γ射线辐照或过氧化氢氧化。将氧化的共聚物与核酸内切酶III或5-羟甲基尿嘧啶-DNA糖基化酶一起孵育,以确定是否形成可修复的产物,或消化成2-脱氧核糖核酸,以确定氧化产物的总补体。对5-甲基胞嘧啶的氧化攻击主要导致胸腺嘧啶乙二醇的形成。聚(dG-dmC)和聚(dA-dT)中胸腺嘧啶二醇的放射性产率相同,表明DNA中的5-甲基胞嘧啶残基和胸腺嘧啶残基一样对辐射诱导的氧化敏感。
Exposure of pyrimidines of DNA to ionizing radiation under aerobic conditions or oxidizing agents results in attack on the 5,6 double bond of the pyrimidine ring or on the exocycllc 5-methyl group. The primary product of oxidation of the 5,6 double bond of thymine is thymine glycol, while oxidation of the 5-methyl group yields 5-hydroxymethyluracil. Oxidation of the 5,6 double bond of cytosine yields cytosine glycol, which decomposes to 5- hydroxycytoslne, 5-hydroxyuracil and uracil glycol, all of which are repaired In DNA byEscherichia coliendonuclease III. We now describe the products of oxidation of 5-methylcytoslne in DNA. Poly(dG-[3H]dmC) was γ-lrradiated or oxidized with hydrogen peroxide in the presence of Fe3+and ascorbic acid. The oxidized co-polymer was Incubated with endonuclease III or 5-hydroxymethyluracil-DNA glycosylase, to determine whether repairable products were formed, or digested to 2-deoxyribonucleosfdes, to determine the total complement of oxidative products. Oxidative attack on 5-methylcytosine resulted primarily in formation of thymine glycol. The radiogenic yield of thymine glycol in poly(dG-dmC) was the same as that In poly(dA-dT), demonstrating that 5-methylcytoslne residues in DNA were equally susceptible to radiation-induced oxidation as were thymine residues.