Figure 4.

Topological transitions during replication of circular DNA. (A) Supercoiled DNA that just started its process of DNA replication. The molecule is still negatively supercoiled and shows right-handed interwinding. The negative supercoiling helps to initiate the process of DNA replication (7). (B) Partially replicated DNA molecule with positive torsional stress causing formation of left-handed interwinding in the unreplicated portion and of right-handed interwinding of precatenanes in the replicated portion. The left-handed interwinding can be easily relaxed by DNA gyrase or by topoisomerase IV. Right-handed interwinding is a poor substrate for the relaxation reaction by Topo IV. (C) Standard representation of freshly replicated molecules forming multiply interlinked DNA catenanes. All crossings in this representation have right-handed chirality but this representation is not the equilibrium form of multiply interlinked DNA catenanes. (D) Schematic presentation of the equilibrium form of multiply interlinked DNA catenanes. Minimization of the elastic energy of multiply interlinked catenanes leads to the formation of a left-handed folding of the entire catenanes (21,78). This folding leads to the apparition of left-handed DNA–DNA juxtapositions that are very good substrates for Topo IV-mediated passages that lead to decrease of DNA catenation. (E) Catenanes with decreasing number of interlinks. Individual rings get supercoiled by DNA gyrase, and left-handed crossings may form in the region deformed by the extrusion of supercoils. (F) Singly interlinked catenanes have a complete freedom to form left-handed juxtapositions. Supercoiling provides the necessary ‘pressure’ leading to unlinking. The representations of DNA molecules at different steps of DNA replication are not shown at the same scale but their size was chosen in order to make important points clear. However, all the drawings correspond to sequential stages of DNA replication of a molecule with 800 bp.