Scientists Capture Two DNA Strands Zipping Together for the First Time

DNA carries a negative electrical charge, and molecules with the same charge repel one another. Yet inside living cells, DNA must sometimes come into close contact and recognise matching sequences — essential for genetic recombination and gene silencing, and a process that can play a role in cancer. Scientists have captured a detailed view of how this happens.

Using atomic force microscopy, a technique that maps surfaces at extremely small scales, researchers watched short DNA pieces align with precision, groove for groove. Simulations tracking atoms and ions around the DNA revealed what makes this possible: positively charged metal ions settle into DNA's grooves, acting as bridges between the two molecules. These divalent, double-charged ions behave like two charged arms, each linking both DNA molecules at once to hold the strands in alignment.

The results give experimental support to an idea proposed about twenty years ago, the “DNA zipper” model. Professor Alexey Kornyshev of Imperial College London and collaborators suggested that salt ions surrounding DNA create alternating charge patterns, helping neighbouring DNA molecules align like two interlocking spiral staircases. Observing this mechanism had proved difficult until now.

Professor Agnes Noy of the School of Physics, Engineering and Technology at the University of York, who co-led the research, said the discovery could help identify genome regions involved in DNA pairing, which may become important when mutations disrupt normal cellular processes and contribute to cancer. Dr Thomas Catley of the University of Sheffield, a co-lead author, said it was incredible to visualise the long-hypothesised mechanism for the first time.

The researchers also found that DNA does not pair equally well along every sequence: some stretches formed much stronger contacts than others, producing hotspots where two helices were especially likely to line up. Because some sequences can be programmed to interact more strongly, the finding could help scientists build customised DNA structures for biotechnology. The study was published in the journal Nucleic Acids Research.