| Project/Area Number |
12480177
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | TOKYO INSTITUTE OF TECHNOLOGY |
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Principal Investigator |
TAKENAKA Akio Tokyo Institute of Technology, Graduate School of Bioscience and Biotechnology, Associate Professor, 大学院・生命理工学研究科, 助教授 (80016146)
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| Co-Investigator(Kenkyū-buntansha) |
SEKIGUCHI Takeshi Iwaki-Meisei University, Faculty of Science and Technology, Professor, 理工学部, 教授 (00108193)
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| Project Period (FY) |
2000 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2000: ¥9,800,000 (Direct Cost: ¥9,800,000)
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| Keywords | DNA / RNA world / Functional nucleic acid / Damaged DNA / X-Ray analysis / I-motif of G-quartets / Octa-stranded helix / Base-paired parallel duplex / base-intercalated duplex / 平行二重らせん / 5-ホルミルウラシル / 5-ホルミルシトシン / シュードウリジン / マキシザイム / RNA / リボザイム / ヘアピンDNA / ロイシルtRNA合成酵素 / RNA結合タンパク質 |
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| Research Abstract |
The project has been successfully performed and revealed the new types of nucleic acid structures, including damaged DNA for mutagenesis, modified nucleotides in RNA, parallel-stranded duplex, bulged-in duplex, inter-and intra-hand-in pocked interaction and base-intercalated duplexes. DNA fragments with d(gcGXYZgc) were investigated by changing the residue at X, Y and Z under different conditions. It has been found that even when it is mutated at X and Y, the sequence always prefer to form a base-intercalated duplex. However, the sequences containing nucleotide except A at Z cannot adopt the base-intercalated duplex. The base-intercalated duplex is quit different from the standard double helix, which was proposed by Watson and Crick 50 years ago. In addition, we found that three base-intercalated duplexes assemble to form a hexa-stranded helix (hexaplex) around cobalt-hexamine cations. When the cation was replace with potassium cation, the fragments assemble to form an octa-stranded he
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lix (octaplex). Furthermore at slightly higher potassium concentration (within physiological conditions), the octaplex is split into just two halves. We have discovered that DNA fragments with sequence gcGA[G]_1Agc form at first base-intercalated duplexes which can associate to form a quadruplex, and finally the two quadruplexes associate to form an octaplex. Recent genome analyses revealed that the human genome contains a huge amount of repetitive sequence's over 50 %, in which a specific sequence similar to the above fragment has been found to be repeated by eight times in VNTR. The octaplex formation described above suggests that the repetitive sequence can fold to form a cluster by double Greek-Key motif. These results were presented in AsCA-2003 meeting and awarded the IUCr prize from International Union of Crystallography. As the several structures found in this project are useful for certain purposes to understand biological phenomena and to develop functional nucleic acids, this project should be extended to further investigations. Less
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