Search and destroy: versatile proteins offer unique structural solutions against uracil in DNA

Despite the simplistic general view of DNA being assembled by only four deoxynucleotides, non-canonical bases constitute a significant part of the genome and play an important role in epigenetics and other physiological processes. Uracil is among the most frequently occurring non-canonical base in DNA and in order to maintain normal cell function, proteins involved in uracil-DNA metabolism require an adequate set of specific binding sites that provide ample distinctive power for nucleobases. Here we present on overview of how this distinction is governed by molecular interactions between side chain and main chain atoms of the protein binding sites and the uracil base.