Topo IIIβ-2 Background Information DNA topoisomerases are nuclear enzymes that regulate the topological structure of DNA by transiently breaking and rejoining DNA strands. Although DNA topoisomerase I (Topo I) and Topo II relax both positive and negative supercoils, Topo III relaxes only negative supercoils. Topo IIIå exists as a long and a short isoform, which are produced by alternative splicing. Topo IIIå, which localizes to the nucleolus, is constitutively expressed and remains at high levels throughout the cell cycle in HL-60 cells. Topo III∫ exists as three isoforms, ∫-1, ∫-2 and ∫-3, also produced by alternative splicing. Topo III∫-1 is expressed in testis, heart, and skeletal muscle, whereas Topo III∫-2 is expressed in thymus, kidney and pancreas.