Characterization of DNA topoisomerase IIα/β heterodimers in HeLa cells

In mammalian cells, DNA topoisomerase II is the product of two distinct genes encoding the α and β isoforms of the enzyme. Besides homodimeric topoisomerase IIα and IIβ, we have recently shown that α/β heterodimers constitute a third population of topoisomerase II in HeLa cells. We found that topoisomerase II heterodimers are not restricted to HeLa cells but exist in different mammalian cell types, and up to 25% of the total topoisomerase IIβ population is involved in heterodimer formation. Studies of topoisomerase II phosphorylation in HeLa cells show that heterodimers are phosphorylated in vivo to a significantly lower level compared to homodimeric α enzymes, but in contrast to the latter neither heterodimers nor topoisomerase IIβ homodimers coprecipitate together with a kinase activity that is able to mediate their phosphorylation. However, both enzymes can still be phosphorylated by exogenously added casein kinase II. The differential phosphorylation of topoisomerase II heterodimers suggests an alternative regulation of this topoisomerase II subclass compared to the homodimeric topoisomerase IIα counterparts.