20 DNA Topoisomerases

Abstract

The double-helical nature of DNA and the anchoring of DNA to nuclear structures result in a number of topological problems during replication and transcription, mainly due to DNA-tracking polymerases and heli-cases. These activities cause the accumulation of positive supercoils ahead of the moving polymerase and negative supercoils behind it (Liu and Wang 1987; Brill and Sternglanz 1988; Giaever and Wang 1988; Wu et al. 1988). (By definition, DNA becomes positively supercoiled when there is a decrease in the number of base pairs per helical turn below 10.3. Likewise, an increase in the number of base pairs per turn above 10.3 results in negatively supercoiled DNA.) The topological imbalance will, if not leveled, ultimately present an impenetrable energy barrier to the tracking protein complexes (Gartenberg and Wang 1992). Enzymes that influence the topological state of DNA thus play a crucial role in controlling the physiological functions of DNA.

In the eukaryotic cell, the topological structure of DNA is modulated by two groups of ubiquitous enzymes known as type I and type II topoisomerases. The enzymes alter the DNA linking number, which is the number of times the two strands are interwound. Type I enzymes (topoisomerase I and the evolutionarily distinct topoisomerase III) inter-convert different topological forms of DNA by breaking and rejoining a single strand of the DNA double helix, changing the linking number in steps of one. Type II enzymes (topoisomerase II), however, catalyze topology changes by reversibly breaking both strands of the DNA double helix, resulting in a linking...