DNA中醛基嘧啶的化学检测

Detection of 5-Formylpyrimidines in DNA Based on Chemoselective Labeling

基因组DNA除A、G、T、C四大经典碱基外,还存在上百种稀有碱基。其中,醛基嘧啶(5-醛基胞嘧啶和5-醛基尿嘧啶)是DNA中天然存在的嘧啶类修饰碱基,在哺乳动物细胞中广泛分布。5-醛基胞嘧啶除参与DNA主动去甲基化过程外,还具备独立的表观遗传功能;而5-醛基尿嘧啶通常被认为是一种基因毒性很高的DNA氧化损伤。根据醛基嘧啶的特征结构,有针对性地开发准确、灵敏和简便的检测方法,从全基因组范围内对他们进行定性、定量和区域定位,是进一步明确这类碱基修饰物调控机制的基础和前提。本文从选择性化学标记的角度总结了近年来醛基嘧啶检测方法的研究进展。

In addition to the four canonical nucleobases of A,G,T and C,hundreds of chemical modifications have been identified in genome DNA.Among them,5-formylpyrimidines,including 5-formylcytosine(5fC)and 5-formyluracil(5fU),are naturally occurring pyrimidine-covalent-modifications and are widely distributed in mammalian cells.Emerging evidence indicates that 5fC not only serves as a key intermediate in active DNA demethylation but also carry independent epigenetic significance;while 5fU was always considered to be an oxidative DNA lesion with high genotoxicity.In order to further understand their regulatory functions,it is necessary to develop accurate,sensitive and facile methods for qualitative,quantitative,and localized detection of 5-formylpyrimidines in the whole genome.In this review,we summarized the recent progress in detecting 5-formylpyrimidines from the perspective of selective chemical labeling.