Fig. 6. Models for the actions of topo IIα in crowded environments created during mitotic chromatid assembly.

a A model for chromatid thickening by collaborative actions of topo IIα and condensins. At the initial step of chromatid assembly, intra-chromatid entanglements are hardly generated because loops are distantly located from one another (step 1). As condensins extrude the loops, the distance between neighboring loops gets shortened (step 2), allowing chromatin-associated topo IIα to generate entanglements between loops (step 3: intra-chromatid entanglement). The resultant intra-chromatid entanglements in turn stabilize chromatid axes and may promote further extrusion of the loops and thickening of the chromatids (step 4). For simplicity, structural changes of an individualized, single chromatid are shown here. b A model for resolution of a pre-assembled sparkler. A sparkler is composed of multiple non-nucleosomal DNAs that are heavily entangled with each other and bound by the linker histone H1.8 (step 1). When topo IIα is added into the reaction, its CTD competes with the linker histone for the non-nucleosomal DNAs and delivers the enzymatic core into the inside of the sparkler (step 2). Topo IIα catalyzes disentanglement reactions there (step 3: inter-chromatid disentanglement), which in turn promotes further dissociation of the linker histone and resolves the sparkler (step 4). For simplicity, condensins’ actions are not depicted here.