Physicists unravel the mechanics of DNA

 (Image: Pixabay CC0) (Image: Pixabay CC0)

A team of physicists at KU Leuven are improving our understanding of how DNA works. Amongst their findings is the proof of the elusive ’twist-bend coupling’, the theory of which was first proposed in 1990. They also found out exactly why our DNA is coiled tighter in some places, while it’s looser in others.

The DNA within our cells is an almost two-metre string of information, stored in a nucleus of only a few micrometres large. The information within those tightly coiled bends and twists needs to be continuously accessed and read - not an easy task.

Scientists have long theorised that DNA has a specific mechanism to it that might make it more accessible. In 1990, a theory was put forward, saying that it’s possible that if you twist DNA, it would also bend automatically. However, to this day, it remained unproven, although scientists studied DNA extensively.

Research also showed that the coils of the DNA string seemed to tighten and loosen in places. We usually think of DNA as a helix-shaped, regular string, but reality somehow seemed different. But why? A team of scientists, composed of Professor Enrico Carlon (KU Leuven), Professor John F. Marko (Northwestern University), and PhD students Enrico Skoruppa and Stefanos K. Nomidis (KU Leuven), now have an answer to that question, along with the proof needed that so-called twist-bend coupling, proposed in 1990, really exists.

Every cell in our body contains about 2 metres of DNA, which is closely packed into a nucleus of a few micrometres. If we stretch out the DNA from the nucleus, we find that it forms a beads-on-a-string structure. The beads here are proteins called histones, around which the DNA is wrapped one and a half times. The DNA and histones together form a nucleosome.  A team of soft matter biophysicists took a closer look at the structure of this nucleosomal DNA. 

Bend-induced twist waves

Since DNA is heavily twisted and bent in the cell, DNA mechanics have been heavily studied by physicists for a long time. Back in 1990, scientists already theorised that the double helix structure of DNA has what is called a ’twist-bend coupling’. In layman’s terms, this means that if you twist a string of DNA, it spontaneously bends and vice versa. 

Now, almost 25 years later, a team of biophysicists at KU Leuven and Northwestern University were able to prove that this twist-bend coupling exists, thus giving us more insight into how DNA responds to mechanical deformations.

By means of mathematical modelling and computer simulations, the team was able to prove that when DNA bends, it also spontaneously twists. 

Furthermore, they were able to prove that our usual representation of DNA as a double helix with a homogeneous structure is, in fact, far too simplistic. A bent double helix actually has ’twist waves’, where some parts are ’overtwisted’ and some parts are ’undertwisted’. This information in itself isn’t new, but theories about why this variation occurred have long credited the effect to the histone proteins in the nucleosomal core.

However, the team was now able to prove that even if you remove the core, the variations remain, proving them to be an inherent characteristic of the DNA string itself. Moreover, they found that these variations occur regularly in the form of waves where the twist varies periodically along the length of DNA. 

Why is this important? 

This research gives more insight into the mechanical properties of DNA and suggests that there are some peculiar ways in which the double helix can be deformed by proteins. A protein could, for instance, untwist the double helix by bending it along an appropriate direction.

Understanding how proteins interact with DNA is of central importance, as the cell uses these interactions to perform a large number of tasks. This work shows us how physics can help us to understand our bodies. 

The researchers received funding from KU Leuven Grant No.IDO/12/08, Research Foundation - Flanders (FWO), the Francqui Foundation, and the US National Institutes of Health (NIH).