1.1. Introduction to Mammalian DNA Base Modifications Genetic information is encoded by the four bases adenine (A), guanine (G), cytosine (C), and thymine (T). Base pairing through hydrogen bonding between the cognate pairs A-T and C-G together within the base stack of the DNA double helix provides the molecular basis for the genetic code.1 It is evident that there are other molecular mechanisms for encoding function within DNA. The major groove and the minor groove each exhibit a hydrogen bonding pattern that enables the primary sequence of the DNA double helix to be read, without being unwound, which is important for sequence-dependent events such as the binding of transcription factors. Furthermore, there are enzyme-dependent chemical modifications to the canonical bases that have the potential to dynamically alter the structure, recognition and function of DNA. Examples of naturally occurring DNA base modifications are shown in Figure ​Figure1.1. There are organisms whose genomes exhibit a substantial level of chemically modified bases, for example in bacteriophages, all or a major proportion of one of the four bases are commonly replaced by a modified base.2 Open in a separate window Figure 1 Structures of modified bases in phage DNAs: (A) α-putrescinylthymine, (B) 5-dihydroxypentyluracil, (C) α-glutamylthymine, and (D) 2-aminoadenine.