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Y-shaped DNA junction structures, also known as three-way junctions (3WJs), are branched nucleic acid motifs where three double-stranded DNA helices meet at a single point (Lilley, 2000). These structures occur naturally as transient intermediates during essential biological processes such as DNA replication, recombination, and repair (Duckworth et al., 2011). In pathological contexts, 3WJs are frequently associated with the expansion of trinucleotide repeats, which are the underlying cause of several neurodegenerative diseases like Huntington's disease (Nakatani et al., 2002). Furthermore, stalled replication forks in rapidly dividing cancer cells often adopt Y-shaped configurations, making them attractive targets for selective therapeutic intervention (Malina et al., 2014). Small molecules, particularly supramolecular metal complexes and certain aminoglycosides, have been developed to bind specifically within the central cavity of the junction (Hannon et al., 2001). By stabilizing these structures, these agents can trigger replication fork collapse or inhibit the enzymatic processing of toxic DNA intermediates, thereby inducing apoptosis in malignant cells (Phongtongpasuk et al., 2013).
Selective binding and stabilization of the three-way junction cavity to inhibit DNA replication, induce replication fork collapse, or prevent the expansion of trinucleotide repeats.
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