Certain sequences of our genome can adopt an unusual structure, known as i-DNA, which is able to change its structure to adapt to the environmental pH.

70 years ago, James Watson and Francis Crick discovered the classic DNA double helix, key to understanding how our genetic information is stored and transmitted. However, much remains to be known about the structure of DNA, especially in relation to flexible regions, capable of adopting various forms depending on their environment. Now, scientists from the “Rocasolano” Institute for Physical Chemistry (IQFR) and the CSIC Institute of Marine Sciences (ICM) have described the curious case of a DNA sequence able to change its structure with the pH. The article is published in The Journal of the American Chemical Society.

This study, carried out in collaboration with the Institute for Research in Biomedicine (IRB) and the University of Barcelona, provides an approximation to the family of structures known as i-DNA, very different from the Watson and Crick double helix. To date, the main characteristics of i-DNA known are its location near the promoter regions of many human genes and its stability in acidic environments.

However, the researchers have not only shown that it can form under physiological conditions, but that it can also adapt its structure to do so. This change in shape could act as a control mechanism to modulate gene expression. The work represents an important advance in the compression of DNA, which is not only the molecule responsible for storing and transmitting genetic information, but is also an essential molecule for future nanotechnology devices.

In this research, the use of the Nuclear Magnetic Resonance spectrometers of the Manuel Rico Laboratory, a Singular Scientific and Technical Infrastructure (ICTS) of the CSIC, has been essential.

I. Serrano-Chacón, B. Mir, L. Cupellini, F. Colizzi, M. Orozco, N. Escaja, C. González. pH-dependent capping interactions induce large-scale structural transitions in i-motifs. J. Am. Chem. Soc. https://pubs.acs.org/doi/10.1021/jacs.2c13043