Two DNA molecules are negatively charged and, according to the laws of electrostatics, ought to repel each other. Yet inside a cell they are able to come almost into direct contact, line up in parallel and form stable contacts.
Now researchers have for the first time managed to see the structure of such an approach directly.
Scientists from the universities of York and Sheffield used high-resolution atomic force microscopy in a liquid medium and combined it with computer modelling of molecular dynamics. In the images, two DNA double helices were positioned side by side over the course of several turns, and their geometry matched with astonishing precision: major grooves aligned opposite major grooves, and minor grooves opposite minor grooves.
The result was a structure resembling a molecular zipper.
Ions become bridges
The key role in this process is played by divalent metal ions — above all magnesium, calcium and nickel.
Since the phosphate backbone of DNA carries a negative charge, two molecules naturally repel each other. Positively charged ions partially compensate for this interaction and can form peculiar bridges between neighbouring helices.
But the mechanism turned out to be more interesting than simple "charge neutralisation".
The modelling showed that ions are able to position themselves inside the major and minor grooves of DNA and create a spatially organised network of contacts. Thanks to this, the two helices do not merely come closer together — they gain the ability to align relative to each other in a specific geometry.
It was precisely such a model of an electrostatic "DNA zipper" that Professor Alexei Kornyshev and his colleagues proposed about twenty years ago. Until now it had largely remained theoretical.
Now researchers have obtained direct structural confirmation of it.
Not all ions act in the same way
Different metals create different types of contacts.
Nickel ions displayed more localised interactions with specific regions of DNA. Magnesium and calcium formed more diverse networks of bonds and could take part in contacts in both the minor and the major grooves.
This means that the chemical environment is able to influence how stably two DNA molecules will remain close to each other and in what manner they will be oriented relative to one another.
However, it is important not to go too far here: the experiment does not show that DNA, on its own and unerringly, recognises an identical sequence solely thanks to ions.
The researchers observed contacts both between similar and between differing sequences. The authors suggest that sequence matching may help to maintain correct alignment and to propagate the contact along the molecule, but this mechanism has yet to be studied in more detail.
Why should DNA come close together at all?
Such interactions may matter for fundamental processes inside the cell: the organisation of chromosomes, the interaction of regions of the genome, and the mechanisms by which DNA molecules must find and compare similar sequences.
The work is also of interest for DNA nanotechnology. The better researchers understand which forces cause two helices to come together and how ions influence this process, the more precisely artificial structures based on DNA can be designed — for example, DNA origami constructs and other programmable nanostructures.
But perhaps the most interesting part of the study lies elsewhere.
At the molecular level, life constantly solves problems that at first glance seem physically impossible. Two negatively charged helices ought to move apart — yet instead they end up side by side, precisely aligning their grooves.
And a few tiny ions help turn repulsion into an ordered contact.
