How copper cations can be used to control DNA structure

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Research perspective written by Henry Day
School of Pharmacy
University of East Anglia, Norwich, UK

How can I explain the importance of this research to the general public?

Watson and Crick showed that our DNA, made up of the four bases A, T, G and C which constitute the genetic code, exists predominantly in a twisted ladder structure called the double helix. Since then, researchers have shown that DNA can actually form many different structures and that these structures can affect their biological function.

One such structure that is formed from mainly C bases is called an i-motif. What role the i-motif plays in biology is still to be understood and therefore investigating what conditions may make it more or less likely to form is very important. Outside of biology, there is a lot of interest in i-motif structures in nanotechnology as they have the ability to fold up or unfold very quickly when acid or base is added. This effectively creates a switch, which is one of the fundamental components of a computer.

This research uses readily available copper salts and an ingredient of household chemicals called EDTA to provide an alternative switch mechanism. It therefore opens the prospect of a wider variety of DNA-based computing applications.

Why is this important for researchers in fields other than chemistry?

This study shows that certain sequences of DNA can be changed from a compact 4-stranded structure called an i-motif to an alternative 2-stranded hairpin like structure in response to copper cations. The study also showed that addition of a chelating agent (EDTA) could be used to reverse the change, and hence provide a switch mechanism. The i-motif itself already has the ability to rapidly change structure in response to changes in pH and this has been studied in a variety of nanotechnology applications such as logic gates, pH sensors inside living organisms and in drug delivery systems. By providing a new alternative switch mechanism, this study increases the range and variety of possible DNA nanotechnology applications such as sensing, logic operations, and DNA computing.

Why is this important for researchers in the same field?

This study demonstrates that cytosine rich sequences of DNA that form i-motif structures under acidic conditions, can be converted to a hairpin-like structure with the addition of copper(II) cations. The change in structure is observed using a combination of circular dichroism, UV difference spectroscopy and NMR. The structural change could be reversed with addition of a slight excess of EDTA to chelate the copper ions and sequential additions of copper and EDTA resulted in repeated changes from i-motif to hairpin and back again. This provides a new insight into what conditions affect i-motif structure and stability, whilst also providing an alternative switch mechanism for controlling i-motif DNA structure.

Original article

Reversible DNA i-motif to hairpin switching induced by copper(II) cations
Henry Albert Day, Elisé Patricia Wright, Colin John MacDonald, Andrew James Gates, Zoë Ann Ella Waller
Chemical Communications, published online 3 August 2015

Acknowledgements

This work was supported by the Royal Society, Novartis and the Biotechnology & Biological Sciences Research Council UK. The original text was published by the Royal Society of Chemistry’s Chemical Communications and is open access.

Originally published at blog.sparrho.com.