Hypermodified bases in DNA

Modified DNA bases are widespread in nature. They can be found in eukaryotes, prokaryotes, and bacteriophages. They may completely replace the standard base or replace only a small fraction. Their substituents vary from simple methyl or hydroxy groups to large moieties like amino acids and multiply hexosylated side chains. This review gives an overview of the modified DNA bases identified thus far, with emphasis on the "very unusual" or hypermodified DNA bases. Although these have been detected mainly in bacteriophages, recent work has shown the presence of a novel hypermodified DNA base in the eukaryote Trypanosoma brucei. We speculate on the biosynthesis and function of this novel base beta-D-glucosyl-hydroxymethyluracil.