Active heterodimers are formed from human DNA topoisomerase IIα and IIβ isoforms

DNA topoisomerase II is a nuclear enzyme essential for chromosome dynamics and DNA metabolism. In mammalian cells, two genetically and biochemically distinct topoisomerase II forms exist, which are designated topoisomerase IIα and topoisomerase IIβ. In our studies of human topoisomerase II, we have found that a substantial fraction of the enzyme exists as α/β heterodimers in HeLa cells. The ability to form heterodimers was verified when human topoisomerases IIα and IIβ were coexpressed in yeast and investigated in a dimerization assay. Analysis of purified heterodimers shows that these enzymes maintain topoisomerase II specific catalytic activities. The natural existence of an active heterodimeric subclass of topoisomerase II merits attention whenever topoisomerases IIα and IIβ function, localization, and cell cycle regulation are investigated.