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Nucleic Acids Res. 2013 Dec;41(22):10556-62. doi: 10.1093/nar/gkt771. Epub 2013 Sep 2.

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

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School of Physical and Mathematical Sciences, Nanyang Technological University, 637371 Singapore, School of Biological Sciences, Nanyang Technological University, 637551 Singapore and Instituto de Química Física Rocasolano, CSIC, 28006 Madrid, Spain.


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.

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