Hydroxyl-radical-induced oxidation of 5-methylcytosine in isolated and cellular DNA.
Hydroxyl-radical-induced oxidation of 5-methylcytosine in isolated and cellular DNA.
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DOI：
10.1093/nar/gku334
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发表时间：
2014-06
影响因子：
14.9
通讯作者：
Wagner JR
中科院分区：
文献类型：
--
作者：
Madugundu GS;Cadet J;Wagner JR
CpG二核苷酸中胞嘧啶的甲基化和氧化去甲基化在细胞分化、胚胎发生和肿瘤发生过程中的基因调控中起着关键作用。尽管其丰度低，5-甲基胞嘧啶（5mC）是哺乳动物细胞中突变的热点。在这里，我们测量了五个氧化产物的5mC连同类似的产品的胞嘧啶和胸腺嘧啶在DNA暴露于电离辐射在含氧水溶液中。这些产物可分为羟基自由基（·OH）在5mC的5，6-双键上的加成产物（乙二醇、乙内酰脲和咪唑烷产物）和H原子从5mC的甲基上的夺取产物（包括5-羟甲基胞嘧啶（5hmC）和5-甲酰基胞嘧啶（5fC））。基于对这些产物的分析，我们表明，在相同序列中，在5mC处的总损伤比在C处的总损伤大约2倍。与胸腺嘧啶和胞嘧啶的类似反应相比，有利于形成5mC的乙内酰脲产物，胸腺嘧啶和胞嘧啶的类似反应有利于形成二醇产物。在特定的ODN双链体中，氧化产物的分布是序列依赖性的。在5mC的情况下，5hmC和5fC的形成约占5mC的·OH诱导氧化产物总量的一半。在辐照细胞中还估计了胸腺嘧啶、胞嘧啶、5mC以及8-氧代-7，8-二氢鸟嘌呤（8oxoG）的几种产物。
The methylation and oxidative demethylation of cytosine in CpG dinucleotides plays a critical role in the regulation of genes during cell differentiation, embryogenesis and carcinogenesis. Despite its low abundance, 5-methylcytosine (5mC) is a hotspot for mutations in mammalian cells. Here, we measured five oxidation products of 5mC together with the analogous products of cytosine and thymine in DNA exposed to ionizing radiation in oxygenated aqueous solution. The products can be divided into those that arise from hydroxyl radical (•OH) addition at the 5,6-double bond of 5mC (glycol, hydantoin and imidazolidine products) and those that arise from H-atom abstraction from the methyl group of 5mC including 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC). Based on the analysis of these products, we show that the total damage at 5mC is about 2-fold greater than that at C in identical sequences. The formation of hydantoin products of 5mC is favored, compared to analogous reactions of thymine and cytosine, which favor the formation of glycol products. The distribution of oxidation products is sequence dependent in specific ODN duplexes. In the case of 5mC, the formation of 5hmC and 5fC represents about half of the total of •OH-induced oxidation products of 5mC. Several products of thymine, cytosine, 5mC, as well as 8-oxo-7,8-dihydroguanine (8oxoG), were also estimated in irradiated cells.
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影响因子：
3.4
作者：
Iijima, Herbert;Patrzyc, Helen B.;Box, Harold C.
通讯作者：
Box, Harold C.
影响因子：
3.7
作者：
Globisch D;Münzel M;Müller M;Michalakis S;Wagner M;Koch S;Brückl T;Biel M;Carell T
通讯作者：
Carell T
影响因子：
15
作者：
Bourdat, AG;Douki, T;Cadet, J
通讯作者：
Cadet, J
影响因子：
3.9
作者：
Collins, AR;Cadet, J;Viña, J
通讯作者：
Viña, J
影响因子：
15
作者：
HAZRA, DK;STSTEENKEN
通讯作者：
STSTEENKEN