摘要
胸腺嘧啶脱氧核糖核酸糖基化酶(thymine DNA glycosylase,TDG)属于单功能尿嘧啶脱氧核糖核酸糖基化酶(uracil DNA glycosidase,UDG)超家族中的成员,在基因组稳定和表观遗传调控中具有双重作用。TDG参与调控DNA甲基化(DNA methylation)和去甲基化(DNA demethylation)。DNA甲基化主要为胞嘧啶(cytosine,C)甲基化,是指胞嘧啶以S-腺苷甲硫氨酸(S-adenosyl Methionine,SAM)为甲基供体,在DNA甲基转移酶(DNA methyltransferase,DNMTs)的作用下,在胞嘧啶第5位碳原子上加上一个甲基,形成5-甲基胞嘧啶(5-methylcytosine,5mC)。5mC广泛存在于哺乳动物基因组中,并在基因组稳定性维持、组织特异性基因沉默、逆转录转座子沉默等诸多生物学过程中发挥重要作用。DNA去甲基化是指5mC还原为C,这个过程也是由DNMTs完成的。DNA去甲基化包括被动去甲基化和主动去甲基化2种途径。被动DNA去甲基化是指在DNA复制过程中,新合成的子链DNA未能维持甲基化状态,导致DNA甲基化的被动稀释(passive dilution);DNA主动去甲基化过程不涉及DNA复制,是指通过TDG等酶的作用去除5mC和5-羧基胞嘧啶(5-hydroxymethylcytosine,5hmC)的氧化产物,即5-甲羟基胞嘧啶(5-formylcytosine,5fC)和5-羧基胞嘧啶(5-carboxylcytosine,5caC)。TDG还通过碱基切除修复途径(base excision repair,BER)切割糖与靶碱之间的N-糖苷键,在纠正错配及损伤的DNA碱基对(base pair,bp)中起重要作用。最近的研究表明TDG还在转录调控、胚胎发育及肿瘤治疗等领域发挥重要作用。本文总结了近年来TDG的研究现状及进展,为进一步的深入研究提供理论支持。
Thymidine DNA glycosidase(TDG) belongs to the superfamily of monofunctional uracil DNA glycosidase,which plays a dual role in genome stability and epigenetic regulation.TDG participates in the regulation of DNA methylation and demethylation.DNA methylation is mainly cytosine(C) methylation,which refers to the formation of 5-methylcytosine(5mC) by adding a methyl to the 5th carbon atom of cytosine under the action of DNA methyltransferase(DNMTs) with S-adenosylmethionine(SAM) as methyl donor.And 5mC is widely distributed in mammalian genomes and plays an important role in maintaining genomic stability,tissue-specific gene silencing,and reverse transcription transposon silencing and many other biological processes.DNA demethylation refers to the reduction of 5mC to C,which is also accomplished by DNMTs.DNA demethylation includes two ways:passive demethylation and active demethylation.Passive DNA demethylation refers to the passive dilution of newly synthesized sub-stranded DNA that fails to maintain its methylation state during DNA replication;Active demethylation of DNA does not involve DNA replication.It refers to the removal of 5-methyl-cytosine(5mC) and 5-carboxy-cytosine(5hmC) oxides,i.e.5-methyl-hydroxy-cytosine(5fC) and5-carboxy-cytosine(5caC),by enzymes such as TDG.TDG also cleaves N-glycoside bonds between sugars and target bases through the base excision repair pathway(BER) and plays an important role in correcting mismatched and damaged DNA base pairs(bps).Recent studies have shown that TDG also plays an important role in transcriptional regulation,embryonic development and tumor therapy.This paper summarizes the research status and progress of TDG in recent years,and provides theoretical support for further in-depth study.
作者
葛长宇
徐鹏
宫榭阳
匡野
GE Chang-yu;XU Peng;GONG Xie-yang(Department of Obstetrics and Gynaecology,the Second Affiliated Hospital of Harbin Medical University,Harbin,Heilongjiang 150086,China)
出处
《中华全科医学》
2019年第2期272-275,共4页
Chinese Journal of General Practice
基金
黑龙江省博士后科研启动金(LBH-Q15099)
作者简介
通信作者:匡野,E-mail:kuangye-blue@163.eom.
