Yebra M J, Bhagwat A S
Department of Chemistry, Wayne State University, Detroit, Michigan 48202-3489, USA.
Biochemistry. 1995 Nov 14;34(45):14752-7. doi: 10.1021/bi00045a016.
Sites of cytosine methylation are known to be hot spots for C.G to T.A mutations in a number of systems, including human cells. Traditionally, spontaneous hydrolytic deamination of 5-methylcytosine to thymine has been invoked as the cause of this phenomenon. We show here that a bacterial cytosine methyltransferase can convert 5-methylcytosine in DNA to thymine and that this reaction creates a mutational hot spot at a site of DNA methylation. The reaction is fairly insensitive to the methyl donor in the reaction, S-adenosylmethionine. In many cancers, the most frequent class of mutations is C to T changes within CG dinucleotides of the tumor suppressor gene p53. Because of the similarities of the reaction mechanisms of mammalian and bacterial enzymes and the physiology of the cancer cells, this reaction is expected to contribute to mutations at CG dinucleotides in precancerous cells.
在包括人类细胞在内的许多系统中，胞嘧啶甲基化位点已知是C.G到T.A突变的热点。传统上，5-甲基胞嘧啶自发水解脱氨生成胸腺嘧啶被认为是这种现象的原因。我们在此表明，一种细菌胞嘧啶甲基转移酶可将DNA中的5-甲基胞嘧啶转化为胸腺嘧啶，并且该反应在DNA甲基化位点产生一个突变热点。该反应对反应中的甲基供体S-腺苷甲硫氨酸相当不敏感。在许多癌症中，最常见的突变类型是肿瘤抑制基因p53的CG二核苷酸内的C到T变化。由于哺乳动物和细菌酶的反应机制以及癌细胞生理学的相似性，预计该反应会导致癌前细胞中CG二核苷酸处的突变。
