Unlinking of supercoiled DNA catenanes by type IIA topoisomerases

It was found recently that DNA catenanes, formed during replication of circular plasmids, become positively (+) supercoiled, and the unlinking of such catenanes by type IIA topoisomerases proceeds much more efficiently than the unlinking of negatively (-) supercoiled catenanes. In an attempt to explain this striking finding we studied, by computer simulation, conformational properties of supercoiled DNA catenanes. Although the simulation showed that conformational properties of (+) and (-) supercoiled replication catenanes are very different, these properties per se do not give any advantage to (+) supercoiled over (-) supercoiled DNA catenanes for unlinking. An advantage became evident, however, when we took into account the established features of the enzymatic reaction catalyzed by the topoisomerases. The enzymes create a sharp DNA bend in the first bound DNA segment and allow for the transport of the second segment only from inside the bend to its outside. We showed that in (-) supercoiled DNA catenanes this protein-bound bent segment becomes nearly inaccessible for segments of the other linked DNA molecule, inhibiting the unlinking.