Pao M M, Liang G, Tsai Y C, Xiong Z, Laird P W, Jones P A
Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, MS#73, 1441 Eastlake Ave., Los Angeles, California, CA 90033, USA.
Oncogene. 2000 Feb 17;19(7):943-52. doi: 10.1038/sj.onc.1203414.
A potential link between DNA repair and de novo methylation of exogenous sequences in colorectal cancer cell lines suggested that cells deficient in mismatch repair (MMR-) had an increased ability to silence the introduced virus promoter by DNA methylation due to the presence of a methylator phenotype (MET+) (Lengauer et al., 1997a). We explored this relationship in more detail and found that although there was a clear difference in the abilities of MMR+ cells to express the viral promoter compared to their MMR- counterparts, this difference was not consistently explained by levels of methylation in the viral promoter. Furthermore, we were unable to distinguish differences between the levels of methylation of six endogenous known CpG islands or 100 random DNA fragments containing CCGG sites within the cells. No consistent differences between the abilities of the cells to methylate the CpG island in exon 2 of the p16 gene were observed after transient demethylation by 5-aza-2'-deoxycytidine nor in the levels of expression of three human methyltransferase enzymes. Our results do not therefore support the existence of mutually exclusive DNA methylation (MET) and DNA repair (MMR) phenotypes. Oncogene (2000) 19, 943 - 952.
结直肠癌细胞系中DNA修复与外源序列从头甲基化之间的潜在联系表明，错配修复缺陷（MMR-）的细胞由于存在甲基化表型（MET+），通过DNA甲基化沉默导入病毒启动子的能力增强（Lengauer等人，1997a）。我们更详细地探讨了这种关系，发现尽管与MMR-细胞相比，MMR+细胞表达病毒启动子的能力存在明显差异，但这种差异并不能始终通过病毒启动子的甲基化水平来解释。此外，我们无法区分细胞内六个内源性已知CpG岛或100个含有CCGG位点的随机DNA片段的甲基化水平差异。在用5-氮杂-2'-脱氧胞苷进行瞬时去甲基化后，未观察到细胞甲基化p16基因外显子2中CpG岛的能力存在一致差异，三种人类甲基转移酶的表达水平也未观察到一致差异。因此，我们的结果不支持存在相互排斥的DNA甲基化（MET）和DNA修复（MMR）表型。《癌基因》（2000年）19卷，943 - 952页。
