Type IA topoisomerases: A simple puzzle?

Type IA topoisomerases are enzymes that can modify DNA topology. They form a distinct family of proteins present in all domains of life, from bacteria to archaea and higher eukaryotes. They are composed of two domains: a core domain containing all the conserved motifs involved in the trans-esterification reactions, and a carboxyl-terminal domain that is highly variable in size and sequence. The latter appears to interact with other proteins, defining the physiological use of the topoisomerase activity. The evolutionary relevance of this topoisomerase-cofactor complex, also known as the “toposome”, as well as its enzymatic consequences are discussed in this review.