Release of N2,3-ethenoguanine from chloroacetaldehyde-treated DNA by Escherichia coli 3-methyladenine DNA glycosylase II.
Release of N2,3-ethenoguanine from chloroacetaldehyde-treated DNA by Escherichia coli 3-methyladenine DNA glycosylase II.
复制标题
大肠杆菌 3-甲基腺嘌呤 DNA 糖基化酶 II 从氯乙醛处理的 DNA 中释放 N2,3-乙烯鸟嘌呤。
DOI：
10.1073/pnas.89.19.9331
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发表时间：
1992
影响因子：
11.1
通讯作者：
Ludlum,DB
中科院分区：
文献类型：
--
作者：
Matijasevic,Z;Sekiguchi,M;Ludlum,DB
人类致癌物氯乙烯在肝脏中代谢为活性中间体，在DNA中形成N2,3-乙基鸟嘌呤。已知N2,3-乙二鸟嘌呤在大肠杆菌DNA复制过程中引起G----A的转变，其形成可能是高等生物的致癌事件。为了研究N2,3-乙基鸟嘌呤的修复作用，我们用[14C]dGTP对DNA进行镍翻译，并用氯乙醛修饰产物，制备了含N2,3-乙基鸟嘌呤的DNA底物。大肠杆菌3-甲基腺嘌呤DNA糖基酶II是从携带质粒pYN1000的细胞中纯化出来的，以蛋白质和时间依赖的方式从氯乙醛修饰的DNA中释放N2,3-乙基鸟嘌呤。这一发现扩大了糖基化酶II的已知底物特异性，包括一个可能与致癌过程有关的修饰碱基。真核细胞中类似的酶活性可能保护它们免受氯乙烯代谢物的暴露。
The human carcinogen vinyl chloride is metabolized in the liver to reactive intermediates which form N2,3-ethenoguanine in DNA. N2,3-Ethenoguanine is known to cause G----A transitions during DNA replication in Escherichia coli, and its formation may be a carcinogenic event in higher organisms. To investigate the repair of N2,3-ethenoguanine, we have prepared an N2,3-etheno[14C]guanine-containing DNA substrate by nick-translating DNA with [14C]dGTP and modifying the product with chloroacetaldehyde. E. coli 3-methyladenine DNA glycosylase II, purified from cells which carry the plasmid pYN1000, releases N2,3-ethenoguanine from chloroacetaldehyde-modified DNA in a protein- and time-dependent manner. This finding widens the known substrate specificity of glycosylase II to include a modified base which may be associated with the carcinogenic process. Similar enzymatic activity in eukaryotic cell might protect them from exposure to metabolites of vinyl chloride.