Research

The first structure of the junction between two types of DNA structures, the i-motif and the double helix, has been published

Scientists from the Rocasolano Institute of Physical Chemistry of CSIC and the University of Barcelona describe for the first time the structure of an interface between regions of DNA with different secondary structures, specifically between the structures called i-DNA and B-DNA. The article appears published in the Journal of the American Chemical Society. It has been almost 70 years since Watson and Crick described the structure of DNA. In a short article, they described the nowadays well-known structure of the double helix, also called duplex or B-DNA. This is the structure normally adopted by the DNA. However, we know now that DNA can form other structures, which scientists usually refer to as non-canonical. In these structures the bases are not necessarily associated in the usual way (adenine with thymine, guanine with cytosine), they are not even composed of two strands, but they can be much more exotic, such as associations between three or four strands. In fact, the most interesting non-canonical structures occur when four strands are associated, giving rise to four-stranded DNA. Two types of four-stranded DNA are known: The so-called G4-DNA or guanine quadruplex, and the i-DNA or i-motif. The first one is formed in guanine rich regions, and the second one in cytosine rich regions of the genome. The function of these non-canonical structures in the cell is not well understood yet, but we think that they are formed transiently when the two strands of the double helix separate one from each other during cellular processes, such as replication or transcription. In recent years the study of these structures has attracted much interest because it is believed that they can be good therapeutic targets, especially for developing new antitumor drugs. If DNA is normally a double helix (B-DNA) and locally forms a different structure, interfaces or junction must occur between different types of DNA structures. We know very little about these regions. In this work we describe the first structure observed to date of a junction between a region of B-DNA and i-DNA. The structure has been determined using the Nuclear Magnetic Resonance (NMR) technique, thanks to the high-field spectrometers of the “Manuel Rico” Laboratory, a unique scientific-technical facility (ICTS) of the CSIC.

Reference: I. Serrano-Chacón, B. Mir, N. Escaja, and C. González. The structure of i-motif/duplex junctions at neutral pH. J. Am. Chem. Soc., 2021. https://doi.org/10.1021/jacs.1c04679