Chemically modified bases exist naturally in genomic DNA. Research into these bases has been invigorated by the discovery of several modified bases in the mammalian genome, in particular 5-methylcytosine and its oxidized derivatives, such as 5-(hydroxymethyl)cytosine and 5-formylcytosine, as well as the enzymes that form and process them, such as the DNA methyltransferases and the ten-eleven translocation enzymes. In this Review, we provide an overview of natural modified bases that have been reported in DNA, our current knowledge of their roles, and the techniques that have enabled us to probe their functions. Analytical methods have been invaluable in helping to advance this field. For example, chemical and enzymatic methods have provided the means to detect and decode modified bases, giving rise to an expanding array of sequencing approaches. Advanced liquid chromatography and tandem mass spectrometry have provided the means to detect and quantify modified bases with very high sensitivity, increasing the prospect of discovering unknown modifications. It is already evident that natural modified DNA bases and their associated enzymology are of fundamental importance to normal biology and to disease. The next decade promises to yield more insights, discoveries and applications from this burgeoning field of research.

化学修饰的碱基天然存在于基因组DNA中。通过发现哺乳动物基因组中几种修饰的碱基，特别是5-甲基胞嘧啶及其氧化衍生物，如5-（羟甲基）胞嘧啶和5-甲酰基胞嘧啶，以及形成和形成酶的方法，对这些碱基的研究得到了积极的发展。处理它们，例如DNA甲基转移酶和十一个十一易位酶。在本综述中，我们概述了DNA中已报道的天然修饰碱基，我们目前对其作用的认识以及使我们能够探究其功能的技术。分析方法对推动这一领域的发展具有不可估量的价值。例如，化学和酶促方法已经提供了检测和解码修饰的碱基的手段，从而产生了越来越多的测序方法。先进的液相色谱和串联质谱法提供了以非常高的灵敏度检测和定量修饰碱基的方法，从而增加了发现未知修饰的前景。显而易见的是，天然修饰的DNA碱基及其相关的酶学对正常生物学和疾病至关重要。未来十年有望从这个新兴的研究领域中获得更多的见识，发现和应用。