SUBSTRATE AND SEQUENCE SPECIFICITY OF A EUKARYOTIC DNA METHYLASE
SUBSTRATE AND SEQUENCE SPECIFICITY OF A EUKARYOTIC DNA METHYLASE
复制标题
DOI：
10.1038/295620a0
复制
发表时间：
1982-01-01
期刊：
影响因子：
64.8
通讯作者：
RAZIN, A
中科院分区：
文献类型：
--
作者：
GRUENBAUM, Y;CEDAR, H;RAZIN, A
在真核DNA中，50-90%的二核苷酸序列C-G是甲基化的。大多数甲基化位点显然位于基因组中的固定位置，并且这种甲基化模式被忠实地世代遗传1。Holliday和Pugh2以及Riggs3提出，甲基部分在DNA复制过程中以一种半保守的方式遗传，这一模型已被DNA介导的基因转移4-6后甲基化DNA整合到小鼠L细胞的实验中得到证实。要使这一机制发挥作用，必须满足两个基本条件：(1)甲基部分必须对称地放置在DNA复制的两条链上；(2)细胞甲基酶必须是DNA复制过程中存在的半甲基化底物所特有的。在这里，我们最终证明，小鼠腹水DNA甲基化酶的最佳体外底物确实是半甲基化的DNA。此外，这种酶似乎只甲基化位于二核苷酸C-G的胞嘧啶残基。
In eukaryotic DNA, 50–90% of the dinucleotide sequence C-G is methylated. Most methylated sites are apparently placed at fixed locations in the genome and this methylation pattern is faithfully inherited from generation to generation1. Holliday and Pugh2and Riggs3have suggested that methyl moieties are inherited in a semi-conservative fashion during DNA replication, and this model has been confirmed by experiments in which methylated DNA was integrated into mouse L-cells following DNA-mediated gene transfer4–6. For this mechanism to operate, two basic requirements must be satisfied: (1) methyl moieties must be symmetrically placed on both strands of the DNA7,8and (2) the cellular methylase should be specific for the hemi-methylated substrate present during DNA replication. Here we demonstrate conclusively that the preferred substratein vitrofor the mouse ascites DNA methylase is indeed hemi-methylated DNA. Furthermore, this enzyme seems to methylate exclusively cytosine residues located at the dinucleotide C-G