DNA Topology: Applications to Gene Expression

Abstract

DNA topology and topological changes are important in DNA packaging, replication, transcription, and recombination. The importance of topology to biology results from the ability of topological changes to manifest as geometric changes in twist, writhe, or both, and therefore to potentiate the formation of wrapped, looped, or melted structures that are high-energy intermediates in DNA transactions. The energetics of topological change and its partitioning into twist and writhe depend on the size and shape of the topological domain. The remodeling of chromatin structure and stability by ATPase motor proteins and by histone acetylases is accompanied by topological changes. Recent results on the mechanisms of remodeling and the challenges in interpretation of topology-based experiments are discussed. Topology can also be manipulated as an experimental variable to serve as a reporter of conformation or as a means of introducing strain into a system. Examples are given from work on DNA looping. Topological change can be transmitted along DNA (action at a distance) even when there is no permanent change in linking number. Dynamic supercoiling can be introduced by tracking proteins such as RNA polymerase (the twindomain model). The dissipation of dynamic supercoiling may be slowed by hydrodynamic resistance to axial rotation conferred by large or bent DNA, or by nucleosomes and other proteins on the DNA. Topoisomerases reduce transcription-induced supercoiling and control the steady-state levels of DNA topological strain. The roles of dynamic supercoiling in transcription initiation and gene regulation at the c-Myc promoter and at several E. coli promoters are discussed.