Steinberg R A, Gorman K B
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Mol Cell Biol. 1992 Feb;12(2):767-72. doi: 10.1128/mcb.12.2.767-772.1992.
CG----TA transitions at CpG sequences account for many human point mutations and are thought to result from hydrolytic deamination of 5-methylcytosine residues in these sites. The gene for regulatory subunit of murine cyclic AMP-dependent protein kinase has two closely linked CpG sites, one of which is a strong hotspot for spontaneous CG----TA mutations leading to cyclic AMP resistance in S49 mouse lymphoma cells. About 5% of mutants with a spontaneous mutation at this CpG site had also acquired a second CG----TA mutation at the nearby CpG site. The two mutations were always at first positions of the Arg codons in which they occurred, and they were always together in a single regulatory subunit allele. Their linked appearance could be attributed to neither the selection conditions nor the preexistence of one mutation in the target cells. The high frequency of these double mutants suggests that their lesions result not from hydrolytic deamination but rather from an endogenous enzymatic mechanism.
CpG序列处的CG到TA的转换占了许多人类点突变，并且被认为是由这些位点上5-甲基胞嘧啶残基的水解脱氨作用导致的。小鼠环磷酸腺苷依赖性蛋白激酶调节亚基的基因有两个紧密相连的CpG位点，其中一个是自发CG到TA突变的强烈热点，会导致S49小鼠淋巴瘤细胞产生环磷酸腺苷抗性。在这个CpG位点发生自发突变的突变体中，约5%在附近的CpG位点也发生了第二个CG到TA突变。这两个突变总是发生在它们所在的精氨酸密码子的第一位，并且总是在单个调节亚基等位基因中同时出现。它们的连锁出现既不能归因于选择条件，也不能归因于靶细胞中一个突变的预先存在。这些双突变体的高频率表明，它们的损伤不是由水解脱氨作用引起的，而是由一种内源性酶机制导致的。
