Cellular Regulation of Mammalian DNA Topoisomerases

This chapter discusses cellular regulation of mammalian DNA topoisomerases, including modifications of DNA topoisomerases and regulation under different physiological states. DNA topoisomerases are enzymes that control and modify the topological states of DNA. Two basic types of DNA topoisomerases have been found in nature. They are distinguished by the number of DNA strands that they transiently break. Type I topoisomerases cause transient single-strand breaks, while type II topoisomerases make transient double-strand breaks. Through these two fundamentally different mechanisms, the topological state of DNA can be modulated. Because the biological functions of the DNA topoisomerase are deeply rooted in the double-helix structure of DNA, DNA topoisomerases, as expected, participate in nearly all biological transactions of DNA, including transcription, recombination, and replication of DNA. Since DNA topoisomerases play such an important role in unraveling the topological strain of DNA generated during DNA replication, transcription, and other vital biological processes involving DNA, cells must have fine control on DNA topoisomerases in order to keep cell functions normal. Each DNA topoisomerase has a characteristic enzyme activity. The importance of DNA topoisomerases for normal cells requires precise control of the activity and function of these enzymes.