Expanding the type IIB DNA topoisomerase family: identification of new topoisomerase and topoisomerase-like proteins in mobile genetic elements

The control of DNA topology by DNA topoisomerases is essential for virtually all DNA transactions in the cell. These enzymes, present in every organism, exist as several non-homologous families. We previously identified a small group of atypical type IIB topoiso-merases, called Topo VIII, mainly encoded by plas-mids. Here, taking advantage of the rapid expansion of sequence databases, we identified new putative Topo VIII homologs. Our analyses confirm the exclu-sivity of the corresponding genes to mobile genetic elements (MGE) and extend their distribution to nine different bacterial phyla and one archaeal superphy-lum. Notably, we discovered another subfamily of topoisomerases, dubbed 'Mini-A', including distant homologs of type IIB topoisomerases and encoded by extrachromosomal and integrated bacterial and archaeal viruses. Interestingly, a short, functionally uncharacterized motif at the C-terminal extremity of type IIB topoisomerases appears sufficient to discriminate between Mini-A, Topo VI and Topo VIII sub-families. This motif could be a key element for understanding the differences between the three sub-families. Collectively, this work leads to an updated model for the origin and evolution of the type IIB topoisomerase family and raises questions regarding the role of topoisomerases during replication of MGE in bacteria and archaea.