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https://doi.org/10.18054/pb.v127i3-4.39372

Potential long-looped G-quadruplexes in the BCL-2 promoter and their implications in gene regulation

Lan Tanko orcid id orcid.org/0009-0005-8303-5149 ; University of Ljubljana, Faculty of Chemistry and Chemical Technology, Ljubljana, Slovenia
David Kranjc orcid id orcid.org/0009-0004-1766-947X ; University of Ljubljana, Faculty of Chemistry and Chemical Technology, Ljubljana, Slovenia
Janez Plavec ; University of Ljubljana, Faculty of Chemistry and Chemical Technology, Ljubljana, Slovenia; National Institute of Chemistry, Ljubljana, Slovenia; EN->FIST Centre of Excellence, Ljubljana, Slovenia *

* Dopisni autor.


Puni tekst: engleski pdf 3.261 Kb

str. 193-206

preuzimanja: 0

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Sažetak

DNA is a highly dynamic polymer composed of nucleotides that typically forms canonical double helix but can also fold into a variety of non-canonical secondary structures under specific conditions. G-quadruplexes (G4s) are an example of such structures that arise from guanine-rich regions and increasingly emerge as key regulators of gene expression. While G4s usually follow a well-established consensus sequence and typically contain short loops, recent evidence indicates that non-standard G4s with long loops may also form and impact gene regulation.
In this article, we examine the potential roles of long-looped G4s in the BCL-2 promoter. We summarize known G4-forming regions, highlighting their distinct topologies and regulatory outcomes, and present structural features that suggest extended loops may cause specific molecular recognition. Using custom computational analysis, we identified putative long-looped G4 motifs that conventional algorithms, such as G4Hunter, often overlook due to loop length penalties. Predictions with RNAfold further suggest that some long-looped candidates exhibit stable hairpin-like loops, supporting their potential to fold under physiological conditions.
We discuss how long loops may enable unique promoter–enhancer interactions, act as additional interaction sites for transcription factors or ligands and expand opportunities for selective targeting by dual-specific ligands. Altogether, we propose that long-looped G4s represent an underexplored layer of gene regulation with the BCL-2 gene as one example of genes potentially including such G4s.

Ključne riječi

DNA; G-quadruplex; long-looped G4s; BCL-2; cancer

Hrčak ID:

347126

URI

https://hrcak.srce.hr/347126

Datum izdavanja:

13.5.2026.

Posjeta: 0 *