DNA double helices observed 'zipping together' for the first time

Scientists have visualised DNA molecules locking together for the first time, providing new insight into how they overcome their negative charges to pair up.

For decades, scientists have hypothesised how two negatively charged DNA molecules can bind together. Researchers from the University of Sheffield and University of York used atomic force microscopy and molecular dynamics simulations to directly visualise DNA molecules interacting with one another. They found that positively charged divalent ions can act as bridges between the two negatively charged DNA molecules, helping to stabilise their pairing.

'To be able to directly visualise this long-hypothesised mechanism for the first time was incredible,' said Thomas Catley, co-first author from the University of Sheffield. 'The advanced imaging techniques at our disposal have allowed us to uncover these key DNA interactions which have implications in many key cellular processes. It opens the door to studying other DNA interactions that, until now, have only existed as theory.'

The team, whose results were published in Nucleic Acids Research, used atomic force microscopy to visualise DNA molecules interacting in the presence of divalent ions including magnesium, calcium and nickel. They then used molecular dynamics simulations to investigate how two DNA molecules pair in the presence of different ions.

They found that strongly paired DNA molecules adopted an ordered alignment in which their major and minor grooves lined up. The authors described this as consistent with a previously proposed 'DNA zipper' model, whereby the positively charged divalent ions help overcome the electrostatic repulsion between the negatively charged DNA molecules. The researchers also found that the location and strength of some ion-mediated interactions varied according to the DNA sequence and the type of ion.

'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,' said Professor Agnes Noy from the University of York, who co-led the study.

The findings provide a possible molecular explanation for how homologous DNA sequences could recognise and align with one another, a process that is important for genetic recombination. The researchers suggest that understanding these interactions could also provide insight into how DNA is packaged inside cells and could eventually contribute to DNA-based biotechnology. However, the experiments used purified DNA rather than living cells, so further research is needed to determine how this mechanism contributes to DNA pairing in cells.