Because objects with the same charge normally push away from each other, DNA molecules might be expected to repel one another. Yet inside living cells, DNA must sometimes come into close contact and recognize matching sequences. These interactions are essential for processes including genetic recombination and gene silencing, and they can also play a role in cancer.
Scientists have now captured a remarkably detailed view of how this happens. Using powerful atomic force microscopy, researchers watched short pieces of DNA align with extraordinary precision, matching one another groove for groove. Computer simulations then revealed what appears to make this close contact possible: positively charged metal ions can settle into the grooves of DNA and serve as tiny molecular bridges between the two molecules.
Professor Agnes Noy, from the School of Physics, Engineering and Technology at the University of York, co-led the research. She said: "This discovery could help researchers identify regions of the genome specially involved in DNA pairing. These regions may become particularly important when mutations disrupt normal cellular processes and contribute to cancer." The results provide experimental support for an idea proposed about twenty years ago called the "DNA zipper" model.
Professor Alexey Kornyshev from Imperial College London and his collaborators originally suggested that salt ions surrounding DNA could produce alternating patterns of electrical charge. Those patterns, according to the model, would help neighboring DNA molecules align with one another much like two interlocking spiral staircases. Until now, directly observing this proposed mechanism had proved difficult.
Scientists Put the "DNA Zipper" to the Test To investigate the process, the researchers scanned DNA samples with atomic force microscopy, a technique capable of mapping surfaces at extremely small scales. These scans allowed the team to construct detailed topographical maps showing how the DNA molecules were positioned. At the same time, sophisticated computer simulations followed individual atoms and ions as they moved around the DNA.
Combining the two approaches gave researchers both a direct view of DNA pairing and a way to understand the molecular forces responsible for it. The simulations showed that double-charged metal ions can effectively behave like two charged arms. Each ion can interact with both DNA molecules at once, forming a bridge across the space separating them and helping hold the two strands in alignment.
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