4 Primer on the Topology and Geometry of DNA Supercoiling

Abstract

I. HISTORICAL INTRODUCTION
In 1953, Watson and Crick proposed their model for the structure of DNA in which two polydeoxyribonucleotides are wound as right-handed helices around each other and around a common axis (Watson and Crick 1953). It was not until 12 years later that Vinograd and his colleagues discovered that the helix axis can also be coiled: This higher-order structure was named supercoiling (Vinograd et al. 1965Vinograd et al. 1968; Vinograd and Lebowitz 1966; Bauer and Vinograd 1968). The key initial observation was that the DNA of the polyoma virus had a higher sedimentation coefficient than an equal length of linear DNA. They concluded that this was due to compaction both by cyclization and by supercoiling and that supercoiling required both DNA strands be free of nicks or gaps. It soon became clear that circular DNA from numerous sources was supercoiled. An important further generalization from the work of Pettijohn, Laemmli, and Worcel, was that even linear DNA can be supercoiled because inside the cell it is constrained into topologically distinct domains (Stonington and Pettijohn 1971; Worcel and Burgi 1972; Pettijohn and Hecht 1974; Drlica and Worcel 1975; Benyajati and Worcel 1976; Paulson and Laemmli 1977). Indeed, virtually all DNA in vivo is supercoiled to approximately the same degree (for review, see Bauer 1978).

From the outset, it was clear that understanding DNA supercoiling required a combination of mathematics and experimentation. A quantitative relationship between supercoiling and the coiling of the strands of the DNA double helix was initially developed by...