| Project/Area Number |
15201042
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied genomics
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| Research Institution | Osaka University (2005)
Kyoto University (2003-2004) |
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Principal Investigator |
NAKATANI Kazuhiko Osaka University, The Institute of Scientific and Industrial Research, Professor, 産業科学研究所, 教授 (70237303)
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| Co-Investigator(Kenkyū-buntansha) |
ZHOU Da-Yang Osaka University, The Institute of Scientific and Industrial Research, Research Associate, 産業科学研究所, 助手 (00324848)
HAGIHARA Masaki Osaka University, The Institute of Scientific and Industrial Research, Research Associate, 産業科学研究所, 助手 (40403000)
TAKEI Fumie Osaka University, The Institute of Scientific and Industrial Research, Technical Staff, 産業科学研究所, 教務職員 (30252711)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥50,180,000 (Direct Cost: ¥38,600,000、Indirect Cost: ¥11,580,000)
Fiscal Year 2005: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2004: ¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2003: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
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| Keywords | Trinucleotide Repeat / Genetic Disease / ミスマッチ / CAGリピート |
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| Research Abstract |
DNA trinucleotide repeats, particularly CXG, are common within the human genome. However, expansion of trinucleotide repeats is associated with a number of disorders, including Huntington's disease, spinobulbar muscular atrophy, and spinocerebellar ataxia1-4. In these cases, the repeat length is known to correlate with decreased age of onset and disease severity5,6. Repeat expansion of (CAG)n, (CTG)n, and (CGG)n trinucleotides may be related to the increased stability of alternative DNA hairpin structures consisting of CXG/CXG triads with X-X mismatches7-11. Small molecule ligands that selectively bound to CAG repeats could provide an important probe for determining repeat length and an important tool for investigating the in vivo repeat extension mechanism. Here we report that naphthyridine-azaquinolone (NA,1) is a ligand for CAG repeats and can be used as a diagnostic tool for determining repeat length. We show by NMR spectroscopy that binding of NA to CAG repeats induces extrusion of a cytidine nucleotide from the DNA helix.
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