Researchers directly visualise two DNA helices zipping together
Researchers at the universities of York and Sheffield have directly observed the ion-mediated mechanism that allows two negatively charged DNA double helices to pair.
For more than two decades, researchers have had a model for how two negatively charged DNA molecules could lock together despite apparently repelling one another. Now, researchers at the universities of York and Sheffield have directly watched the process happen: two DNA double helices pairing and zipping together.
The images were captured using high-powered atomic-force microscopy, which allowed the researchers to visualise the helices as they came together rather than infer the interaction from its effects. The University of York’s account of the work says this is the first time two DNA double helices have been imaged pairing in this way.
The apparent contradiction is resolved by divalent metal ions. DNA carries a negative charge, but positively charged ions can sit between the molecules and act as molecular bridges, helping hold the two helices together. Computer simulations indicated that the ions nestle into grooves in the DNA, creating the contacts that make the pairing possible.
The researchers identified ions including nickel, magnesium and calcium in this bridging role. The Sheffield researchers’ description of the finding says the helices were directly visualised locking together despite their identical negative charges, confirming the DNA-zipper mechanism proposed more than two decades ago.
The pairing is not uniform along the molecules. Some DNA sequences form stronger hotspots for the interaction, suggesting that the order of the building blocks helps determine where the helices are most likely to meet and remain attached. That gives the zipper model more detail than a simple picture of two strands being pulled together by charge-neutralising ions.
The result is a particularly clean example of microscopy settling a long-standing molecular question: the researchers did not merely observe that metal ions affect DNA pairing, but connected those ions to visible bridges between two complete double helices. The finding may aid further research into DNA pairing, chromosome organisation and mutations associated with cancer.