Identification of toposome, a novel multisubunit complex containing topoisomerase IIα

Topoisomerase IIα plays essential roles in chromosome segregation. However, it is not well understood how topoisomerase IIα exerts its function during mitosis. In this report, we find that topoisomerase IIα forms a multisubunit complex, named toposome, containing two ATPase/helicase proteins (RNA helicase A and RHII/Gu), one serine/threonine protein kinase (SRPK1), one HMG protein (SSRP1), and two pre-mRNA splicing factors (PRP8 and hnRNP C). Toposome separates entangled circular chromatin DNA about fourfold more efficiently than topoisomerase IIα. Interestingly, this decatenation reaction yields knotted circles, which are not seen in reactions provided with monomeric circular DNA. Our results also show that interaction among toposome-associated proteins is highest in G₂/M phase but drastically diminishes in G₁/S phase. These results suggest that toposome is a dynamic complex whose assembly or activation is subject to cell cycle regulation.