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Thursday, February 3, 2011

A new kind of base-pairing

Left: Watson-Crick base pair; Right: Hoogsteen base pair (A = Adenine, U = Uracil, found in RNA).

We’re all familiar with the double helix form of DNA. However, that’s not the only shape DNA ever takes. Hashim Al-Hashimi led a team from the University of Michigan in identifying and observing an alternate form of DNA.

Normally, the DNA bases adenine (A), thymine (T), guanine (G) and cytosine (C) pair up in a specific way to create what’s known as a ‘Watson-Crick’ double helix. By using modified nuclear magnetic resonance (NMR), the team was able to observe a different kind of pairing called ‘Hoogsteen’ base pairs. Although this structure had been observed before, Hoogsteen base pairs were thought to occur only in DNA that is damaged or bound to certain proteins or drugs. Al-Hashimi and his team showed that this is not the case, in fact, DNA can spontaneously, though briefly, flip into the alternative orientation. The changes were too ephemeral to have been seen by conventional NMR. Al-Hashimi’s innovation was to adapt NMR for use in studying transient solutions that exist for only milliseconds.

It’s not clear what the significance of these structures may be. It’s possible that these DNA structures may add levels of information and complexity to the DNA code, much as methylation and other epigenetic changes do.

You can watch DNA flipping between these forms below: