The fluidity of torsional stress along the DNA chain
The fluid changes in conformation and free energy of the DNA helix are influenced by many processes including the binding of proteins, some of which may have a regulatory function. Thus binding of a protein in one position along a DNA chain could result in alterations in the topology of the DNA, and hence changes in free energy availability, both locally and at some distance from the binding site. Changes in torsional energy may serve as an indicator of the state of the surrounding helix. For example, a decrease in torsional energy could indicate a break in a DNA chain, since the broken chain would be free to untwist and torsional stress would be released. Changes in torsional energy could therefore aid detection of such DNA damage.
When the DNA helix must be ‘opened’, by unpairing of its constituent bases, to allow access of replication or transcription machinery, the local untwisting of the helix must be accommodated by increased positive twisting of the flanking DNA helix. If we consider transcription, the RNA polymerase molecule is fixed as the helix is progressively unwound to allow the enzyme access. As a result, positive DNA twisting increases ahead of the transcription machinery, increasing the level of positive supercoiling, as shown in Figure 12. Positive supercoiling presents a considerably higher energy barrier to strand separation, a process that has to occur in order for transcription to continue. At the same time, the region behind the transcription machinery relaxes to accommodate the unwound region, effectively undergoing negative twisting and forming negative supercoils. Such torsional differences highlight the effect of the structure of DNA on its processing. Management of the altered torsional stresses that result from the processing of DNA occurs through the action of specific enzymes, the topoisomerases, which we will now discuss.