Fig. 1

Twin supercoiling domain model. This is the model proposed by Liu and Wang (1987) and supported by numerous independent experiments. Core RNA polymerase is engaged in transcript elongation: mRNA, ribosomes and nascent polypeptide are omitted for clarity. As the coupled transcription-translation complex moves from left to right, the DNA template ahead becomes over wound (positively supercoiled plectonemes) while the DNA behind becomes under wound (negatively supercoiled plectonemes). This situation will halt transcription as the machinery jams because: (a) the domains of supercoiled DNA cannot be removed by supercoil diffusion due to the presence of topological barriers (black spheres at the ends of the DNA) and (b) the bulky transcription-translation complex cannot rotate around the DNA to relieve the torsional tension in the duplex DNA. Instead, DNA gyrase will remove the positive supercoils while the negative ones are relaxed by DNA topoisomerases I and/or IV. Interference with these relaxation processes can result in undesirable outcomes, such as R-loop formation (Fig. 2). Topological barriers can arise due to head-to-head transcription complex collisions and by collisions between converging replisomes and transcription complexes; they can be produced by nucleoprotein complexes and by distortions (e.g. sharp bends) in the DNA duplex. The oval arrows at the bottom of the figure represent possible rotational solutions to these topological problems: each of these solutions is ruled out (red lines) because rotation of the DNA and/or the transcription complex cannot occur, for the reasons summarised in (a) and (b) above