Abstract
Regulation of gene expression is one of the fundamental functions of a living organism. It is not sufficient to make a desired cell component through specific mechanism(s), since the production must be quantitatively, locally, and temporally controlled and concerted for granting harmonic evolution of the cell cycle. Hence, the need for a finely tuned effective and dependable mechanism of regulation. Among possible strategies, a type of control mediated by DNA structural rearrangements has lately received great attention. This was mainly amplified toward G-quadruplex (G4) because of the apparent simplicity of the construct and the in-depth structural experience earned when DNA biological functions, besides the genomic information, were not known yet. Unrestrained transcription rate is related to genetic instability and increased DNA repair. These conditions correlate to cancer progression and neurological disorders, which prompted the idea of using selective G4 ligands to interfere with the expression of disease-associated genes. Unfortunately (or fortunately) the issue of specific G4 recognition proved to be overly complicated in vivo by the plasticity of the nucleic acid, able to assume several conformations with comparable energy, hence biologically significant. As a result, we are still waiting for a G4-directed drug to reach the market. To drive the attention toward more focused strategies, particular arrangements in which more than one G4 moiety contributes to complex affinity and selectivity are being considered. Finally, the recently established G4 participation in epigenetic processes opens new hopefully successful drug design perspectives.
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Acknowledgments
This work was supported by AIRC (grant IG 2021 - ID26474, PI CS), CERIC ERIC (grants No. 20207052 and 20202174) and European Union-Next GenerationEU (PNRR M4C2-Investimento 1.4- CN00000041).
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Palumbo, M., Sissi, C. (2023). DNA Structural Elements as Potential Targets for Regulation of Gene Expression. In: Sugimoto, N. (eds) Handbook of Chemical Biology of Nucleic Acids. Springer, Singapore. https://doi.org/10.1007/978-981-16-1313-5_39-1
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