Like charges normally repel one another, yet DNA molecules must pair up inside living cells to carry out essential biological processes, including genetic recombination, gene silencing and the development of cancer. Using high-powered atomic force microscopy, a team led by researchers from the University of York observed short DNA fragments matching up with exact precision, groove for groove. Advanced computer simulations revealed that positively charged metal ions act as tiny molecular bridges, nestling inside the grooves to lock the two strands together. The study was published in Nucleic Acids Research.
“This discovery could help researchers identify regions of the genome specially involved in DNA pairing,” explained study co-leader Professor Agnes Noy. “These regions may become particularly important when mutations disrupt normal cellular processes and contribute to cancer.”
The findings confirm a 20-year-old theory known as the “DNA zipper” model, originally proposed by Professor Alexey Kornyshev from Imperial College London, which suggested that surrounding salt ions create alternating charge patterns, allowing DNA molecules to line up like interlocking spiral staircases. To test this, the team used atomic force microscopy to scan DNA samples and build topographical maps, while detailed computer models tracked the movement of individual atoms and ions. They discovered that double-charged metal ions act like two charged arms, holding both DNA strands simultaneously across the gap.
Thomas Catley, co-lead author from the University of Sheffield, said: “It was incredible to be able to directly visualize the long-hypothesized mechanism for the first time. The advanced imaging techniques at our disposal are allowing us to uncover these key DNA interactions which have implications in many key cellular processes.”
The team also discovered that DNA pairing is not uniform. Certain DNA sequences form much stronger contacts than others, creating specific hotspots where two helices are particularly likely to align. Beyond cancer research, these programmable interactions could eventually help engineers design custom DNA structures for future biotechnology applications.
“This discovery could help researchers identify regions of the genome specially involved in DNA pairing,” explained study co-leader Professor Agnes Noy. “These regions may become particularly important when mutations disrupt normal cellular processes and contribute to cancer.”
The findings confirm a 20-year-old theory known as the “DNA zipper” model, originally proposed by Professor Alexey Kornyshev from Imperial College London, which suggested that surrounding salt ions create alternating charge patterns, allowing DNA molecules to line up like interlocking spiral staircases. To test this, the team used atomic force microscopy to scan DNA samples and build topographical maps, while detailed computer models tracked the movement of individual atoms and ions. They discovered that double-charged metal ions act like two charged arms, holding both DNA strands simultaneously across the gap.
Thomas Catley, co-lead author from the University of Sheffield, said: “It was incredible to be able to directly visualize the long-hypothesized mechanism for the first time. The advanced imaging techniques at our disposal are allowing us to uncover these key DNA interactions which have implications in many key cellular processes.”
The team also discovered that DNA pairing is not uniform. Certain DNA sequences form much stronger contacts than others, creating specific hotspots where two helices are particularly likely to align. Beyond cancer research, these programmable interactions could eventually help engineers design custom DNA structures for future biotechnology applications.