Intramolecular Higher Order Packing of Parallel Quadruplexes Comprising a G:G:G:G Tetrad and a G(:A):G(:A):G(:A):G Heptad of GGA Triplet Repeat DNA

GGA triplet repeats are widely dispersed throughout eukaryotic genomes and are frequently located within biologically important regions such as gene regulatory regions and recombination hot spot sites. We determined the structure of d(GGA)4 (12-mer) under physiological conditions and founded the for...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-07, Vol.278 (30), p.28147-28153
Main Authors: Matsugami, Akimasa, Okuizumi, Tomoyuki, Uesugi, Seiichi, Katahira, Masato
Format: Article
Language:English
Subjects:
Circular Dichroism
Crystallography, X-Ray
DNA - chemistry
DNA - metabolism
Guanine - chemistry
Ions
Magnetic Resonance Spectroscopy
Models, Molecular
Nucleic Acid Conformation
Potassium - metabolism
Repetitive Sequences, Nucleic Acid
Sodium - metabolism
Telomere - ultrastructure
Trinucleotide Repeats
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Summary:GGA triplet repeats are widely dispersed throughout eukaryotic genomes and are frequently located within biologically important regions such as gene regulatory regions and recombination hot spot sites. We determined the structure of d(GGA)4 (12-mer) under physiological conditions and founded the formation of an intramolecular parallel quadruplex for the first time. Later, a similar architecture to that of the intramolecular parallel quadruplex was found for a telomere DNA in the crystalline state. Here, we have determined the structure of d(GGA)8 (24-mer) under physiological conditions. Two intramolecular parallel quadruplexes comprising a G:G:G:G tetrad and a G(:A):G(:A):G(:A):G heptad are formed in d(GGA)8. These quadruplexes are packed in a tail-to-tail manner. This is the first demonstration of the intramolecular higher order packing of quadruplexes at atomic resolution. K+ ions, but not Na+ ones, are critically required for the formation of this unique structure. The elucidated structure suggests the mechanisms underlying the biological events related to the GGA triplet repeat. Furthermore, in the light of the structure, the mode of the higher order packing of the telomere DNA is discussed.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M303694200