TAILIEUCHUNG - Báo cáo khoa học: Structure of a human telomeric DNA sequence stabilized by 8-bromoguanosine substitutions, as determined by NMR in a K+ solution

The structure of human telomeric DNA is controversial; it depends upon the sequence contexts and the methodologies used to determine it. The solution structure in the presence of K + is particularly interesting, but the structure is yet to be elucidated, due to possible conformational heterogen-eity. | ỊFEBS Journal Structure of a human telomeric DNA sequence stabilized by 8-bromoguanosine substitutions as determined by NMR in a K solution Akimasa Matsugami1 Yan Xu2 Yuuki Noguchi2 Hiroshi Sugiyama2 and Masato Katahira1 3 4 1 Supramolecular Biology InternationalGraduate Schoolof Arts and Sciences Yokohama City University Japan 2 Graduate Schoolof Sciences Kyoto University Japan 3 RIKEN Yokohama Japan 4 PRESTO Yokohama Japan Keywords 8-bromoguanosine NMR quadruplex structure telomere Correspondence M. Katahira Supramolecular Biology International Graduate School of Arts and Sciences Yokohama City University 1-7-29 Suehiro-cho Tsurumi-ku Yokohama 230-0045 Japan Fax 81 45 508 7361 Tel 81 45 508 7213 E-mail katahira@ Received 7 March 2007 revised 13 May 2007 accepted 15 May 2007 doi The structure of human telomeric DNA is controversial it depends upon the sequence contexts and the methodologies used to determine it. The solution structure in the presence of K is particularly interesting but the structure is yet to be elucidated due to possible conformational heterogeneity. Here a unique strategy is applied to stabilize one such structure in a K solution by substituting guanosines with 8-bromoguanosines at proper positions. The resulting spectra are cleaner and led to determination of the structure at a high atomic resolution. This demonstrates that the application of 8-bromoguanosine is a powerful tool to overcome the difficulty of nucleic acid structure determination arising from conformational heterogeneity. The obtained structure is a mixed-parallel antiparallel quadruplex. The structure of telomeric DNA was recently reported in another study in which stabilization was brought about by mutation and resultant additional interactions Luu KN Phan AT Kuryavyi V Lacroix L Patel DJ 2006 Structure of the human telomere in K solution an intramolecular 3 1 G-quadruplex scaffold. J Am Chem Soc 128 9963-9970 . The .

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