Removal of O6-methylguanine from DNA by human liver fractions.
Removal of O6-methylguanine from DNA by human liver fractions.
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通过人肝脏组分从 DNA 中去除 O6-甲基鸟嘌呤。
DOI：
10.1073/pnas.79.17.5162
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发表时间：
1982
影响因子：
11.1
通讯作者：
Montesano,R
中科院分区：
文献类型：
--
作者：
Pegg,AE;Roberfroid,M;vonBahr,C;Foote,RS;Mitra,S;Bresil,H;Likhachev,A;Montesano,R
在使用甲基化DNA作为底物的体外试验中，人肝组分被证明能够催化O 6-甲基鸟嘌呤的去除。去除的量与加入的蛋白质的量成正比，并且O 6-甲基鸟嘌呤的损失发生在DNA中鸟嘌呤和蛋白质中S-甲基半胱氨酸的化学计量形成的情况下。这表明，人类肝脏含有一种蛋白质，类似于以前在暴露于烷化剂的细菌中发现的蛋白质。这种蛋白质作为一种甲基转移酶，将DNA中的O 6-甲基鸟嘌呤的完整甲基转移到该蛋白质上的半胱氨酸残基上。啮齿类动物的肝脏中也存在类似的活性，但发现人类肝脏在进行这种反应时的活性约为10倍。相比之下，人类和大鼠肝脏提取物在催化另一种甲基化产物7-甲基鸟嘌呤从烷基化DNA中丢失方面没有差异。肝脏是暴露于外源性潜在烷化剂（如二甲基亚硝胺）后最有可能发生烷化剂化的器官。目前的研究结果表明，人类肝脏有一个显着的能力，修复O 6-甲基鸟嘌呤的DNA，这已被牵连作为一个关键的产品在致癌和诱变。
In in vitro assays using methylated DNAs as substrates, human liver fractions were shown to be able to catalyze the removal of O6-methylguanine. The amount of removal was proportional to the amount of protein added, and the loss of O6-methylguanine occurred with stoichiometric formation of guanine in the DNA and S-methylcysteine in protein. This indicates that human liver contains a protein similar to that previously found in bacteria exposed to alkylating agents. This protein acts as a transmethylase, transferring the intact methyl group from O6-methylguanine in DNA to a cysteine residue on that protein. A similar activity is present in rodent liver, but it was found that human liver was about 10 times more active in carrying out this reaction. In contrast, there was no difference between the human and rat liver extracts in catalyzing the loss of another methylation product, 7-methylguanine, from alkylated DNA. The liver is the organ most likely to be alkylated after exposure to exogenous potential alkylating agents such as dimethylnitrosamine. The present results show that human liver has a significant capacity to repair O6-methylguanine in DNA, which has been implicated as a critical product in carcinogenesis and mutagenesis.