Dynamics of strand passage catalyzed by topoisomerase II

DNA topoisomerase II is a homodimeric molecular machine that uses ATP hydrolysis to untangle DNA by passing one double-stranded DNA duplex (T-segment) through another double-stranded duplex (G-segment). However, despite extensive studies, the dynamics of ATP-dependent T-transport is still not very clear. Here, based on the proposal that transport of the T-segment through the transiently cleaved G-segment and the opened C-gate of the enzyme is via a free diffusion mechanism, the dynamics of T-transport are studied theoretically. Our results show that, to complete passage of the strand with nearly 100% efficiency, the C-gate is required to open by a width that is only slightly larger than the width of DNA duplex and for a time shorter than 100 micros in the presence of several k (B) T binding affinities of the T-segment for the B' domains. The results are implied by our understanding of the opening and closing dynamics of the C-gate. Moreover, the dependence of chemomechanical coupling efficiency on degrees of DNA supercoiling by gyrases can also be explained by using our results. On the basis of these theoretical results and previous experimental data, a modified two-gate model for chemomechanical coupling of the topoisomerase II enzyme is proposed.