Felicia chen-wu memorial lecture:

“thoughts on the plectonemic nature of the dna double helix”

James C. Wang

Department of Molecular and Cellular Biology, Harvard University,

Cambridge, Massachusetts 02138 U.S.A.


In a letter to James D. Watson on May 12, 1953, a month after the publication of the celebrated Watson-Crick structure, Max Delbrück wrote: “…..I am willing to bet that the plectonemic coiling of the chains in your structure is radically wrong…..” To Delbrück, the plectonemic DNA double helix structure would pose “insuperable” difficulties if the coiled DNA strands are to separate during semiconservative replication.

Even though more than quarter of a century would pass before the final confirmation of the Watson-Crick structure, by X-ray crystallography, it was already clear in 1963 that the two strands in a DNA must be intertwined to a certain extent. Therefore there must be a way for the DNA strands to untangle. The first part of this lecture provides a brief introduction to the “DNA untanglement problem” raised by Delbrück, and discusses why some of the seemingly plausible ways of solving this problem were dismissed. The second part describes how nature solved the DNA untanglement problem: three distinct subfamilies of DNA topoisomerases were to evolved, and all problems arising from the plectonemic nature of the DNA double helix can be solved by these enzymes. These three rather ingenious solutions are not yet perfect, however; they all came with inherent price tags, as demonstrated by their being the targets in some of nature’s chemical and biological warfare.

Historically, the discovery of the DNA topoisomerases was closely linked to the study of different forms of DNA rings. The third and final part of this lecture discusses how some of the unique topological features of DNA rings, or loops, are utilized in cellular transaction of DNA. These features are also rooted in the plectonemic double helix structure. It is clear that nature, other than solving problems closely linked to such features, is equally ingenious in exploiting them.