Invited Speaker

Hue Sun Chan

Selective segment passages at hooked and twisted juxtapositions consistently rationalize the decatenating, unknotting, and supercoil-suppressing actions of type-II topoisomerases

The mathematical basis of the hypothesis that type-II topoisomerases (topo-II) disentangle by recognizing specific DNA juxtapositions was investigated by lattice polymer models. We determined the statistical relationship between the local geometry of a juxtaposition of two chain segments and the global topological state of the model DNA conformations. Selective segment passages at "hooked" and "twisted" juxtapositions in the model can lead to dramatic decreases in catenanes and knots, similar to those observed in topo-II experiments. Remarkably, the logarithmic unknotting potential of a juxtaposition geometry in our model correlates almost perfectly with its logarithmic decatenating potential, entailing a power-law scaling between the two potentials with an exponent similar to that deduced experimentally from the behaviors of topo-IIs from various organisms. Selective segment passages at "hooked" and "twisted" juxtapositions suppress supercoiling in our polymer model as well. Analyses of such model processes provided a physical rationalization for the experimental findings that topo-IIs are more effective in decatenating and unknotting small DNA circles than large DNA circles yet topo-IIs are less effective in suppressing supercoils in small DNA circles.