The effect of molecular crowding conditions on DNA secondary structures formed by the PIM1 gene

Date

2025-8-26

Author

Göller, İrem

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G-quadruplexes formed within biologically important regions of DNA, such as promoter sequences, play key roles in regulating gene expression. The recent discovery of G-quadruplex-duplex hybrid structures in the promoter region of the PIM1 oncogene, which is overexpressed in triple-negative breast cancer (TNBC), further underscores their biological relevance. Recently, the formation of G-quadruplex, duplex and i-motif structures in the PIM1 gene has been investigated in dilute aqueous solution conditions. However, the intracellular environment is highly crowded with biomacromolecules and it is known that such molecular crowding affects the structure and function of DNA. Accordingly, the effect of molecular crowding on the PIM1 secondary structures under different environmental conditions was investigated in this thesis. CD results demonstrated that molecular crowding alters the G-quadruplex and duplex conformations depending on the cation type, whereas i-motif structures remained mostly unaffected. Molecular crowding was found to increase the stability of G-quadruplex structure while decreasing the stability of i-motif and duplex structures. Furthermore, for the first time the effect of molecular crowding on the interactions between the anticancer drug agent Doxorubicin (Dox) and PIM1 secondary structures was investigated in this thesis and the binding of Doxorubicin to PIM1 structures under the crowding conditions was confirmed. This study demonstrates the difference between the effect of crowded and dilute environments on DNA structures, and its interactions with the ligands, highlighting the importance of considering molecular crowding in such investigations.

Subject Keywords

G-quadruplex, I-motif, DNA, PIM1 gene, Molecular crowding

URI

https://hdl.handle.net/11511/116038

Collections

Graduate School of Natural and Applied Sciences, Thesis