Roles of DNA topoisomerases in chromosome segregation and mitosis

DNA topoisomerases are highly specialized nuclear enzymes that perform topological changes in the DNA molecule in a very precise and unique fashion. Taking into account their fundamental roles in many events during DNA metabolism such as replication, transcription, recombination, condensation or segregation, it is no wonder that the last decade has witnessed an exponential interest on topoisomerases, mainly after the discovery of their potential role as targets in novel antitumor therapy. The difficulty of the lack of topoisomerase 11 mutants in higher eukaryotes has been partly overcome by the availability of drugs that act as either poisons or true catalytic inhibitors of the enzyme. These chemical tools have provided strong evidence that accurate performance of topoisomerase 11 is essential for chromosome segregation before anaphase, and this in turn constitutes a prerequisite for the development of normal mitosis. In the absence of cytokinesis, cells become polyploid or endoreduplicated. (C) 2002 Elsevier Science B.V. All rights reserved.