Schmutte C, Jones P A
Thomas Jefferson University, Kimmel Cancer Center, Philadelphia, PA 19107, USA.
Biol Chem. 1998 Apr-May;379(4-5):377-88. doi: 10.1515/bchm.1998.379.4-5.377.
It is now generally accepted that the presence of 5-methylcytosine (5mC) in human DNA has both a genetic and an epigenetic effect on cellular development, differentiation and transformation. First, 5mC is more unstable than its unmethylated counterpart cytosine. Hydrolytic deamination of 5mC leads to a G/T mismatch and subsequently, if unrepaired, to a C-->T transition mutation. Sites of DNA methylation are mutational hotspots in many human tumors. Second, DNA methylation of promoter regions is often correlated with the down regulation of the corresponding gene. Both of these effects have fundamental consequences for basic functions of the cell like cellular differentiation, the development of cancer and possibly other diseases, and on the evolutionary process. Recent hypotheses also propose a role for methylation in the process of aging. In this review we will describe recent findings and hypotheses about the function of 5mC in DNA with the focus on its involvement in human carcinogenesis.
现在人们普遍认为，人类DNA中5-甲基胞嘧啶（5mC）的存在对细胞发育、分化和转化具有遗传和表观遗传效应。首先，5mC比其未甲基化的对应物胞嘧啶更不稳定。5mC的水解脱氨会导致G/T错配，随后，如果未修复，会导致C→T转换突变。DNA甲基化位点是许多人类肿瘤中的突变热点。其次，启动子区域的DNA甲基化通常与相应基因的下调相关。这两种效应都对细胞的基本功能（如细胞分化、癌症及其他可能疾病的发展）以及进化过程产生根本性影响。最近的假说还提出甲基化在衰老过程中发挥作用。在本综述中，我们将描述关于DNA中5mC功能的最新发现和假说，重点关注其在人类致癌作用中的参与情况。
