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Crystal structure of parallel quadruplexes from human telomeric DNA

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Date
2002-06-20
ICR Author
Neidle, Stephen
Author
Parkinson, GN
Lee, MPH
Neidle, S
Type
Journal Article
Metadata
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Abstract
Telomeric ends of chromosomes, which comprise noncoding repeat sequences of guanine-rich DNA, are fundamental in protecting the cell from recombination and degradation(1). 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(2-4), which may be involved in the structure of telomere ends(5). 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(2,4,6). 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.
URI
https://repository.icr.ac.uk/handle/internal/2731
DOI
https://doi.org/10.1038/nature755
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  • Other ICR Research
Language
eng
License start date
2002-06-20
Citation
NATURE, 2002, 417 pp. 876 - 880
Publisher
NATURE PUBLISHING GROUP

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