Gary N. Parkinson, Michael P. H. Lee & Stephen Neidle

The Cancer Research UK Biomolecular Structure Unit, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK

Correspondence and requests for materials should be addressed to S.N. (e-mail: s.neidle@icr.ac.uk).

Atomic coordinates for the 12-mer strand and the 22-mer quadruplex have been deposited in the Protein and Nucleic Acid Data Banks (accession codes: 12 mer, 1K8P and UD0016 respectively; 22-mer, 1KF1 and UD0017 respectively).

Telomeric ends of chromosomes, which comprise noncoding repeat sequences of guanine-rich DNA, are fundamental in protecting the cell from recombination and degradation. Disruption of telomere maintenance leads to eventual cell death, which can be exploited for therapeutic intervention in cancer. Telomeric DNA sequences can form four-stranded (quadruplex) structures, which may be involved in the structure of telomere
ends. Here we describe the crystal structure of a quadruplex formed from four consecutive human telomeric DNA repeats and grown at a K⁺ concentration that approximates its intracellular concentration. K⁺ ions are observed in the structure. The folding and appearance of the DNA in this intramolecular quadruplex is fundamentally different from the published Na⁺-containing quadruplex structures. All four DNA strands are parallel, with the three linking trinucleotide loops positioned on the exterior of the quadruplex core, in a
propeller-like arrangement. The adenine in each TTA linking trinucleotide loop is swung back so that it intercalates between the two thymines. This DNA structure suggests a straightforward path for telomere folding and unfolding, as well as ways in which it can recognize telomere-associated proteins.

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