Good review articles are pure gold, especially when they’re open access. Here is one. See, “DNA topoisomerases: Advances in understanding of cellular roles and multi-protein complexes via structure-function analysis.”

A biochemistry friend who works with topoisomerases told me years ago that Crick and Watson realized, very early on, that the winding double helix of DNA would cause all kinds of nasty tangles. In their second Nature paper (1953), however, on the “Genetical Implications of the Structure of Deoxyribonucleic Acid” (May 30), they noted:

Since the two chains in our model are intertwined, it is essential for them to untwist if they are to separate. As they make one complete turn around each in 34 A., there will be about 150 turns per million molecular weight, so that whatever the precise structure of the chromosome a considerable amount of uncoiling would be necessary. It is well known from microscopic observation that much coiling and uncoiling occurs during mitosis, and  though this is on a much larger scale it probably reflects similar processes on a molecular level. Although it is difficult at the moment to see how these processes occur without everything getting tangled, we do not feel that this objection will be insuperable.

I love that last clause: “…we do not feel that this objection will be insuperable.” No, indeed, because organisms are solving their topological problems, somehow. Not to worry. The system as a whole will have the functional difficulty covered.

It’s design triangulation, although both Crick and Watson would scream No. That’s okay; their actions in publication belie their personal philosophies.