Repetitive blocks of guanine- and cytosine-rich sequences, such as those occurring in centromeric and telomeric DNA regions and promoter regions of protein coding genes, have ability to form G- and C-quadruplex structures, respectively. These non-B DNA structures are involved in more than 40 pathological human conditions including cancer. From a biophysical point of view, a common property to both G- and C-rich sequences is their inherent sensitivity to non-specific, physical-chemical environmental factors promoting their conformational polymorphism. Despite significant effort, motivated by both biological significance and biotechnological and biomedical applications of these non-B DNA motifs, the mechanistic nature of the environmentally induced effects remains poorly understood. The mechanistic insight and revealing of relationships between the DNA sequence and its folding topology in relation to its environment is essential for both rational design of novel nanomaterials and ways for their manipulations as well as for related biomedical applications. In this project, we propose systematic investigations of the influence of non-specific physical-chemical factors on structure of the DNA quadruplexes. In parallel, we propose characterization of these structures under the physiological conditions in vivo using state-of-the-art method of in-cell NMR spectroscopy. The acquired information will help to identify physiologically relevant structures of G- and C-quadruplexes.
Field of science
- /natural sciences/biological sciences/genetics and heredity/dna
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