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J. Biol. Chem., Vol. 278, Issue 30, 28147-28153, July 25, 2003

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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^*

Akimasa Matsugami , Tomoyuki Okuizumi , Seiichi Uesugi  and Masato Katahira   ¶

From the Department of Environment and Natural Sciences, Graduate School of Environment and Information Sciences, Yokohama National University, 79-7 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan and the RIKEN Genomic Sciences Center, Tsurumi, Yokohama 230-0045, Japan

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.

Received for publication, April 9, 2003

The atomic coordinates and structure factors (code 1OZ8) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ Supported by Grants-in-aid for Scientific Research (numbers 12470487 and 15030214) and the Protein 3000 Project of the Ministry of Education, Culture, Sports, Science and Technology of Japan. To whom correspondence should be addressed. Tel.: 81-45-339-4264; Fax: 81-45-339-4264; E-mail: masakata{at}ynu.ac.jp.

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