Inverted strand polarity yields thermodynamically stable G-quadruplexes and prevents duplex formation within extended DNA.

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dc.citation.issue37
dc.citation.volume15
dc.contributor.authorChilton B
dc.contributor.authorRoach RJ
dc.contributor.authorEdwards PJB
dc.contributor.authorJameson GB
dc.contributor.authorHale TK
dc.contributor.authorFilichev VV
dc.coverage.spatialEngland
dc.date.accessioned2024-10-15T19:25:26Z
dc.date.available2024-10-15T19:25:26Z
dc.date.issued2024-08-27
dc.description.abstractDNA G-quadruplexes (G4) formed in guanine-rich sequences play a key role in genome function and maintenance, interacting with multiple proteins. However, structural and functional studies of G4s within duplex DNA have been challenging because of the transient nature of G4s and thermodynamic preference of G-rich DNA to form duplexes with their complementary strand rather than G4s. To overcome these challenges, we have incorporated native nucleotides in G-rich sequences using commercially available inverted 3'-O-DMT-5'-O-phosphoramidites of native nucleosides, to give 3'-3' and 5'-5' linkages in the centre of the G-tract. Using circular dichroism and 1H nuclear magnetic resonance spectroscopies and native gel electrophoresis, we demonstrate that these polarity-inverted DNA sequences containing four telomeric repeats form G4s of parallel topology with one lateral or diagonal loop across the face of the quadruplex and two propeller loops across the edges of the quadruplex. These G4s were stable even in the presence of complementary C-rich DNA. As an example, G4 assemblies of inverted polarity were shown to bind to the hinge region of Heterochromatin Protein 1α (HP1α), a known G4-interacting domain. As such, internal polarity inversions in DNA provide a useful tool to control G4 topology while also disrupting the formation of other secondary structures, particularly the canonical duplex.
dc.description.confidentialfalse
dc.edition.edition07 October 2024
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/39246343
dc.identifier.citationChilton B, Roach RJ, Edwards PJB, Jameson GB, Hale TK, Filichev VV. (2024). Inverted strand polarity yields thermodynamically stable G-quadruplexes and prevents duplex formation within extended DNA.. Chem Sci. 15. 37.
dc.identifier.doi10.1039/d3sc05432b
dc.identifier.eissn2041-6539
dc.identifier.elements-typejournal-article
dc.identifier.issn2041-6520
dc.identifier.number15417
dc.identifier.piid3sc05432b
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/71719
dc.languageeng
dc.publisherThe Royal Society of Chemistry
dc.publisher.urihttps://pubs.rsc.org/en/content/articlelanding/2024/sc/d3sc05432b
dc.relation.isPartOfChem Sci
dc.rights(c) 2024 The Author/s
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.en
dc.titleInverted strand polarity yields thermodynamically stable G-quadruplexes and prevents duplex formation within extended DNA.
dc.typeJournal article
pubs.elements-id491442
pubs.organisational-groupOther
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