Final Report Summary - ECOPOD (Environmentally Controlled Polymorphism of non-B DNA structures)
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-tetraplex 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 systematically investigated influence of non-specific physical-chemical factors on structure of the DNA tetraplexes. Conformational properties of a broad spectrum of G- and C-rich DNA oligonucleotides emulating telomeric and centromeric regions of eukaryotic genomes as well as promoter regions of (onco)genes from human genome were studied under various in vitro and in-vivo/ex vivo conditions. The results obtained in the framework of the project resulted in seven publications in peer-reviewed international journals. The results were also presented at three international conferences in a form of poster presentations and invited lectures. In the framework of the project, independent research group (led by the fellow) has been established at the host institution. The project related topics were embedded into three teaching courses at the host institution. In the project period, 13 students concluded their studies under the supervision of the fellow.
In this project, we systematically investigated influence of non-specific physical-chemical factors on structure of the DNA tetraplexes. Conformational properties of a broad spectrum of G- and C-rich DNA oligonucleotides emulating telomeric and centromeric regions of eukaryotic genomes as well as promoter regions of (onco)genes from human genome were studied under various in vitro and in-vivo/ex vivo conditions. The results obtained in the framework of the project resulted in seven publications in peer-reviewed international journals. The results were also presented at three international conferences in a form of poster presentations and invited lectures. In the framework of the project, independent research group (led by the fellow) has been established at the host institution. The project related topics were embedded into three teaching courses at the host institution. In the project period, 13 students concluded their studies under the supervision of the fellow.