**4. Uracil**

Uracil is a base analogue of thymine and is found in both DNA and RNA (**Figure 1**). As a pyrimidine nucleotide it has an amino acid group at the 2′ position and a carboxy group at the 5′ position. U and T are equivalent in their information storage, transmission and their base pairing with adenine.

In DNA, U is present in pyrimidine dimers, tri- and tetradiphosphate conjugates, DNA repair intermediates and DNA damage-based U incorporation. It is classified as an antimetabolite, which means it can block enzymes that participate in cellular metabolism, where its incorporation into DNA has several biological and pharmacological effects.

Uracil's presence in DNA has been identified to be an important key intermediate in both adaptive and innate immunity (see Section 4.2). In adaptive immunity, U is introduced into DNA by the enzyme activation-induced deaminase (AID), where in B lymphocytes its presence modulates the antibody binding site or initiation of Ig isotype switching [29, 30]. In innate immunity, U in DNA serves as an intermediate in the restriction of viral pathogens with the assistance of the family of APOBEC polynucleotide deaminases, where there is a C:U hypermutation of the viral genome leading to its degradation [31].

Beyond these positive immunity roles of U in DNA, the DNA incorporation of U can negatively impact the cellular functionality of the genetic information storage

system, destabilize the Watson-Crick DNA helical structure, inhibit DNA replication, cell growth and development, highlighting the importance of cellular mechanisms to detect and remove inappropriate uracil from DNA.
