Topoisomerase II (Topo II) is a nuclear enzyme that regulates the topological states of DNA by transient breakage and rejoining double-stranded DNA, catalyzing the decatenation and unknotting of topologically linked DNA circles and the relaxation of supercoiled DNA. In mammalian cells, Topo II consists of two isozymes, Topo IIa (170 kDa) and Topo IIB (180 kDa). Expression and localization of each isoform are distinct and stage specific during the cell cycle. Topo IIB is expressed constantly throughout cell cycle, whereas the expression of Topo IIa is cell cycle-regulated, peaking in G2 to M phase and declining to a minimal level at the end of M phase. It is considered that Topo IIa plays an essential role in cell proliferation, especially during late S to M phase.