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Bulged G-quadruplexes in the human genome: identification and characterization of a novel type of non-canonical G-quadruplex
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Kuznetsov, Vladimir
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Fall 2023
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2023-11
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Abstract
G-quadruplexes (G4s) are secondary nucleic acid structures that are abundant in the human genome and have been linked to numerous physiological and pathological conditions. The underlying DNA sequence is a major determinant of the topology and stability of folded G4s. G4s containing bulges are a subpopulation of G4-like structures, whose genome-wide localization and functions are still unknown. Our study focuses on addressing this gap. We utilized a data-driven approach to establish models for the computational genome-wide prediction of potential sites of bulge containing G4 formation (pG4-BS). We also showed that the majority of human protein coding genes contain these pG4-BS, especially in their promoters and exon-intron junctions, suggesting roles in transcription and splicing processes. Furthermore, we validated our computational models using both thermodynamic assays and datasets derived from high-throughput
technologies. We also showed that bulged G4s and R-loops, another type of secondary nucleic acid structure, show strong association with each other, hinting at functional interplay between these structures.