Moving one DNA double helix through another by a type II DNA topoisomerase: the story of a simple molecular machine

Abstract

The discovery of the double helix structure of DNA led immediately to questions on the mechanics of unravelling its intertwined strands during replication. If a parental DNA is to be duplicated into two progeny molecules by separating its two strands and copying each, then the strands must untwine rapidly during replication (Watson & Crick, 1953).That DNA indeed replicates in such a semiconservative fashion was soon demonstrated by the Meselson–Stahl experiment (1958). At first, it appeared that the unravelling of the intertwined strands should not pose an insurmountable mechanical problem. The two strands at one end of a linear DNA, for example, can be pulled apart with concomitant rotation of the double-stranded portion of the molecule around its helical axis. If the strands of a DNA double helix are to separate at an estimated replication rate of 100000 base pairs (bp) per minute, then the speed of this rotation would be 10000 revolutions per minute from the 10 bp per turn helical geometry of the double helix. This speed, though impressive, seemed reasonable: owing to the slender rod-like shape of the double helix, the estimated viscous drag for this rotational motion is actually rather modest (Meselson, 1972).