Structure of the human telomere in Na+ solution : an antiparallel (2+2) G-quadruplex scaffold reveals additional diversity

• Main Authors: Lim, Kah Wai, Ng, Veronica Chinn Min, Martin-Pintado, Nerea, Heddi, Brahim, Phan, Anh Tuan
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2014
• Subjects: DRNTU::Science::Biological sciences::Human anatomy and physiology::Deoxyribonucleic acids
• Online Access: https://hdl.handle.net/10356/79374; http://hdl.handle.net/10220/18590
• Institution: Nanyang Technological University

Single-stranded DNA overhangs at the ends of human telomeric repeats are capable of adopting four-stranded G-quadruplex structures, which could serve as potential anticancer targets. Out of the five reported intramolecular human telomeric G-quadruplex structures, four were formed in the presence of K+ ions and only one in the presence of Na+ ions, leading often to a perception that this structural polymorphism occurs exclusively in the presence of K+ but not Na+. Here we present the structure of a new antiparallel (2+2) G-quadruplex formed by a derivative of a 27-nt human telomeric sequence in Na+ solution, which comprises a novel core arrangement distinct from the known topologies. This structure complements the previously elucidated basket-type human telomeric G-quadruplex to serve as reference structures in Na+-containing environment. These structures, together with the coexistence of other conformations in Na+ solution as observed by nuclear magnetic resonance spectroscopy, establish the polymorphic nature of human telomeric repeats beyond the influence of K+ ions.