Snakes & Ladders

My fascination with this topic began after meeting artist Mark Curtis in 2017. Driven by his interest in nature and the depiction of space, Curtis began an investigation into structure of DNA in 1995. The resulting artwork was later used for a Royal Mail 'Millennium Collection' stamp, commemorating the discovery of DNA.

The following is taken from New Scientist, 16 May 1998 - Deconstructing DNA:

After many attempts, he found he couldn't make sense of the two and three-dimensional representations he found in textbooks. They seemed to contradict one another. Frustration finally forced him back to what he refers to as "geometrical first principles", and in the manner of Renaissance perspectival artists such as Paolo Uccello, he began by making careful scale drawings of DNA.

DNA has ten base pairs to each turn of the helix, so, using these centuries-old methods, Curtis began with a decagon-a 10-sided figure. He then placed a pentagon for each base around it. The pentagon is the only regular shape that can fit round a decagon in this way without leaving any space. And according to Curtis, this figure of 10 pentagons oriented about a decagon is the only geometrical configuration that enables one to create a helix with the known dimensions of DNA. Add some thickness to each of the pentagons, and the 10 pentagons telescope out to form a helix. To build a structurally sound double helix, Curtis reasoned that he would need not just one pentagon, but two joined together. With this insight he was finally able to produce the drawings and paintings that he had originally planned.

This kind of reasoning may seem obscure by modern standards. But for Curtis, it established that a double helix of 10 turns had to be made of twinned pentagons. At this point in his work, he was still thinking in terms of the traditional Watson and Crick structure. But he faced a contradiction: in the standard Watson and Crick chemistry, the base pairs join through hexagonal regions in their structures. Then came Curtis's moment of truth: "I sat down on the sofa one night and I thought, hang on a second, the molecular structures of the bases also have pentagons in them. And here was I, with two pentagons, building a consistent helix that conformed to the dimensions of the DNA double helix." By connecting the bases differently, Curtis found that he could naturally form pairs of pentagons in each base pair. "It was placed in my lap. I wasn't trying to prove anybody wrong. I wasn't even thinking then that they've got it wrong. I was just playing, like artists play."

It was later brought to Curtis' attention that he had inadvertently created base pairs discovered by Karst Hoogsteen in 1959.

There is a growing body of work on Hoogsteen base pairs. The following is from a 2019 paper - Infrared Spectroscopic Observation of a G–C+ Hoogsteen Base Pair in the DNATATA‐Box Binding Protein Complex Under Solution Conditions:

Hoogsteen DNA base pairs (bps) are an alternative base pairing to canonical Watson–Crick bps and are thought to play important biochemical roles. Hoogsteen bps have been reported in a handful of X‐ray structures of protein–DNA complexes. However, there are several examples of Hoogsteen bps in crystal structures that form Watson–Crick bps when examined under solution conditions. Furthermore, Hoogsteen bps can sometimes be difficult to resolve in DNA:protein complexes by X‐ray crystallography due to ambiguous electron density and by solution‐state NMR spectroscopy due to size limitations. Here, using infrared spectroscopy, we report the first direct solution‐state observation of a Hoogsteen (G–C+) bp in a DNA:protein complex under solution conditions with specific application to DNA‐bound TATA‐box binding protein. These results support a previous assignment of a G–C+ Hoogsteen bp in the complex, and indicate that Hoogsteen bps do indeed exist under solution conditions in DNA:protein complexes.