Fig. 7. Model for how TOP1 safeguards transcription output levels.

As DNA helix is being unwound during transcription (a), DNA helical stress concomitantly increases with transcription (b) and topological structures such as plectonemes are being formed ahead and behind the transcription bubble, if torsional stress is not sufficiently relieved by catalytic activity of TOP1. Additional TOP1 proteins, through simultaneous DNA binding at both its DNA binding sites, could preferentially bind at juxtaposed DNA helices on the plectonemes and form compact DNA structures that could further torsionally constrain the DNA (c). This built up of superhelical stress in DNA leads to deceleration in transcription (d), thereby preventing further increase in supercoiling. The decrease in transcription subsequently reduces the amount of helical stress being generated (e) and the eventual lifting of the restraint placed on transcription. This then allows transcription to increase again (f), thereby preventing transcription from falling below appropriate levels. The cycle then repeats.