Controlling Topology of a Telomeric G-quadruplex DNA With a Chemical Cross-link
| dc.contributor.author | Chilton B | |
| dc.contributor.author | Edwards PJB | |
| dc.contributor.author | Jameson GB | |
| dc.contributor.author | Hale TK | |
| dc.contributor.author | Filichev VV | |
| dc.date.accessioned | 2025-07-08T03:22:49Z | |
| dc.date.available | 2025-07-08T03:22:49Z | |
| dc.date.issued | 2025-06-18 | |
| dc.description.abstract | DNA G-quadruplexes (G4s) are noncanonical structures formed in guanine-rich sequences. Within the human genome, they are nonrandomly distributed and influence DNA replication, gene expression, and genome maintenance. Numerous proteins involved in these processes have been identified as G4-binding proteins. However, the interaction of proteins with G4s in the context of double-stranded DNA in vitro has been difficult to study due to the transient nature of G4s in the presence of complementary DNA. To overcome this challenge, introducing internal covalent cross-links between distant nucleotides within the DNA sequence may promote pre-folding of G4 structures, thereby shifting the thermodynamic equilibrium toward G4-formation. We used a Cu(I)-catalyzed azide–alkyne cycloaddition to create a cross-link between 2′-O-propargylguanosine and N<sup>6</sup>-azidoethyl-2′-deoxyadenosine in the DNA telomeric sequence (TAG<inf>3</inf>T)<inf>2</inf>. A cross-link between G3 and A8 reinforced the parallel G4 topology that was stable in the presence of complementary DNA. Moreover, even in the presence of its complementary strand, this cross-linked G4 recruited the parent native DNA (TAG<inf>3</inf>T)<inf>2</inf> to form a hybrid G4. These results suggest that cross-linking provides a useful tool for stabilizing noncanonical DNA structures in the presence of complementary strands, enabling their study within the context of genomic DNA. | |
| dc.identifier.citation | Chilton B, Edwards PJB, Jameson GB, Hale TK, Filichev VV. (2025). Controlling Topology of a Telomeric G-quadruplex DNA With a Chemical Cross-link. Chemistry A European Journal. | |
| dc.identifier.doi | 10.1002/chem.202501467 | |
| dc.identifier.eissn | 1521-3765 | |
| dc.identifier.elements-type | journal-article | |
| dc.identifier.issn | 0947-6539 | |
| dc.identifier.uri | https://mro.massey.ac.nz/handle/10179/73167 | |
| dc.publisher | Wiley-VCH GmbH, Germany | |
| dc.relation.isPartOf | Chemistry A European Journal | |
| dc.rights | (c) 2025 The Author/s | |
| dc.rights | CC BY 4.0 | |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
| dc.title | Controlling Topology of a Telomeric G-quadruplex DNA With a Chemical Cross-link | |
| dc.type | Journal article | |
| pubs.elements-id | 501422 | |
| pubs.organisational-group | Other |
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