Mapping and elucidating the function of modified bases in DNA

Abstract:: 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.

Themes