INTRODUCTION The faithful replication and segregation of chromosomes as part of the cell division cycle requires that topological changes be imposed upon cellular DNA. Interconversion of different topo-logical forms of DNA is catalysed by DNA topoisomerases, a family of enzymes classified according to their catalytic mechanism of action. Type I enzymes introduce transient singlestranded breaks into DNA, pass an intact single strand of DNA through the broken strand, and then re-ligate the break. Type II enzymes, in contrast, make transient double-stranded breaks into one segment of DNA and pass an intact duplex through the broken DNA, before resealing the break. Topoisomerases are ubiquitousenzymes charged with the task of resolving topological problems which arise during the various processes of DNA metabolism, including transcription, recombination, replication and chromosome partitioning during cell division (reviewed by Wang, 1985; Sternglanz, 1989; Austin and Fisher, 1990; Osheroff et al., 1991; Gasser et al., 1992). As a result of performing this vital role, topoisomerases are necessary for the viability of all organisms from unicellular bacteria to humans. This intriguing family of enzymes has also aroused considerable interest since many antibacterial and antitumour drugs target topoisomerases and influence key steps in their catalytic cycle (reviewed in Beck and Danks, 1991; Capranico and Zunino, 1992; Fernandes et al., 1993; Pommier, 1993; Beck et al., 1993). In this review article, we shall concentrate on a discussion of the structure, mechanism of action and functions of the type II topoisomerase enzymes, particularly those from eukaryotic cells. However, it will be necessary, for comparison, to review briefly the type I enzymes.

DNA TOPOLOGY The topological features of DNA that require definition are linking number, knotting and catenation. Linking number describes the number of times two DNA strands cross each other when projected onto a plane. Knotting and catenation are respectively the irreducible entanglement of a single DNA molecule, and the linking of two or more DNA molecules in which at least one strand of each duplex is in the form ofa closed ring. As a consequence of the mechanistic differences between type I and type II topoisomerases, linking number changes catalysed by type I enzymes are in steps of one and those catalysed by type II enzymes are in steps oftwo. Linking number is always an integer and changes can be achieved only by breakage and resealing of either one or two DNA strands. Linking number is dictated by two geometric functions, twist and writhe, which define different conformations which are adopted by closed-circular DNA in response to supercoiling changes. Twist is the extent to which the two complement&ry strands of DNA coil about the axis of the DNA helix, whereas writhe is the coiling of the helical axis in space. The sum of twist