New structures of DNA discovered, for a better understanding of the mechanisms of immune response activation
|Prof. Janez Plavec, Director of the Slovenian CERIC facility at the National Institute of Chemistry in Ljubljana, significantly contributed to an important achievement that was published in the prestigious scientific journal Nature Communications. The field is that of DNA research and represents a breakthrough, since it discovers hitherto unknown structures of DNA and thus improves the understanding of DNA and the mechanism of immune response activation.
Structural studies with the use of solution-state nuclear magnetic resonance (NMR) spectroscopy have shown that oligonucleotides containing AGCGA repeats fold into structures that belong to a new structural family which we named AGCGA-quadruplexes. The structural core of the family is comprised out of four AGCGA repeats that form quartet planes. AGCGA-quadruplexes contain unusual structural elements such as GCGC and AGCGA quartets and are additionally stabilized with noncanonical base pairs. To the best of our knowledge, we have described GAGA-quartets formed by two G-A pairs in N1-N7 carbonyl amino geometry for the first time. G-G base pairs in N1-carbonyl symmetric geometry formally form loop regions and connect quartets inside AGCGA-quadruplexes. It is especially interesting that even though guanine residues are very common in oligonucleotides that form AGCGA-quadruplexes they in turn do not contain G-quartets and are insensitive to the presence of different cations such as Na+, K+ and NH4+. This property makes the AGCGA-quadruplex structural family unique compared to the related and more widely known family of G-quadruplexes. With bioinformatics studies we have shown that AGCGA rich sequences are found in regulatory regions of 39 human genes responsible for basic cellular processes that are related to neurological disorders, cancer and abnormalities in bone and cartilage development. With the use of NMR and CD spectroscopy we have confirmed that 46 oligonucleotides found in regulatory regions of the above mentioned 39 human genes fold into AGCGA-quadruplexes. The results of the study are published in the journal Nature Communications.