Cellular roles of DNA topoisomerases: a molecular perspective

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Abstract
This review examines the cellular functions of the DNA topoisomerases from a mechanistic point of view. The following points are summarized. Classification of DNA topoisomerases into four subfamilies IA, IB, IIA and IIB, and the unique mechanistic features of each subfamily. The topological problems of various cellular transactions of DNA, such as replication and transcription, and the plausible roles of different subfamilies of DNA topoisomerases in each of these processes. The presence of at least one IA enzyme in all known living organisms, and plausible roles of this subfamily that cannot be fulfilled by any of the other subfamilies of DNA topoisomerases. The DNA topoisomerases presumably evolved to solve the topological problems of DNA as it became longer and longer or ring-shaped. These elegant solutions nevertheless introduce weak spots into intracellular DNA because of the necessity of transiently breaking DNA strands. So, the DNA topoisomerases might have become the unwitting targets of a plethora of natural and synthesized compounds.