Zhu Jian-Kang
Institute for Integrative Genome Biology and Department of Botany and Plant Sciences, University of California, Riverside, CA 92521, USA.
Annu Rev Genet. 2009;43:143-66. doi: 10.1146/annurev-genet-102108-134205.
Active DNA demethylation is involved in many vital developmental and physiological processes of plants and animals. Recent genetic and biochemical studies in Arabidopsis have demonstrated that a subfamily of DNA glycosylases function to promote DNA demethylation through a base excision-repair pathway. These specialized bifunctional DNA glycosylases remove the 5-methylcytosine base and then cleave the DNA backbone at the abasic site, resulting in a gap that is then filled with an unmethylated cytosine nucleotide by as yet unknown DNA polymerase and ligase enzymes. Evidence suggests that active DNA demethylation in mammalian cells is also mediated at least in part by a base excision repair pathway where the AID/Apobec family of deaminases convert 5-methylcytosine to thymine followed by G/T mismatch repair by the DNA glycosylase MBD4 or TDG. This review also discusses other possible mechanisms of active DNA demethylation, how genome DNA methylation status might be sensed to regulate the expression of demethylase genes, and the targeting of demethylases by small RNAs.
主动DNA去甲基化参与植物和动物许多重要的发育和生理过程。最近在拟南芥中的遗传学和生物化学研究表明，一个DNA糖基化酶亚家族通过碱基切除修复途径促进DNA去甲基化。这些特殊的双功能DNA糖基化酶去除5-甲基胞嘧啶碱基，然后在无碱基位点切割DNA主链，产生一个缺口，随后由未知的DNA聚合酶和连接酶用未甲基化的胞嘧啶核苷酸填补该缺口。有证据表明，哺乳动物细胞中的主动DNA去甲基化至少部分也是由碱基切除修复途径介导的，其中脱氨酶的AID/Apobec家族将5-甲基胞嘧啶转化为胸腺嘧啶，随后由DNA糖基化酶MBD4或TDG进行G/T错配修复。本综述还讨论了主动DNA去甲基化的其他可能机制、如何感知基因组DNA甲基化状态以调节去甲基化酶基因的表达，以及小RNA对去甲基化酶的靶向作用。
