DNA molecules can coil and bend in space, leading to changes in topology, including formation of negative or positive supercoils. For example, as discussed in Chapter 4, local unwinding of a DNA duplex whose ends are fixed causes stress that is relieved by supercoiling. The enzymes that control the topology of DNA function at several different steps in replication in both prokaryotic and eukaryotic cells. In this section we describe the two different classes of topoisomerases and their role in DNA replication.