期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1982
卷号：79
期号：17
页码：5162-5165
DOI：10.1073/pnas.79.17.5162
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
