| Project/Area Number |
15201046
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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 |
Living organism molecular science
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| Research Institution | Kyoto University |
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Principal Investigator |
SUGIYAMA Hiroshi Kyoto University, Graduate School of Science, Professor, 大学院・理学研究科, 教授 (50183843)
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| Co-Investigator(Kenkyū-buntansha) |
BANDO Toshikazu Kyoto University, Graduate School of Science, Assistant Professor, 大学院・理学研究科, 助手 (20345284)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥27,820,000 (Direct Cost: ¥21,400,000、Indirect Cost: ¥6,420,000)
Fiscal Year 2004: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Fiscal Year 2003: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
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| Keywords | DNA / Z form DNA / photoreaction / H abstraction / DNA conformation / DNA probe / B-Z transition / 5-halouracil / 修飾塩基 |
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| Research Abstract |
DNA is polymorphic and exists in a variety of distinct conformations. Duplex DNA can adopt a variety of sequence-dependent secondary structures, which range from the canonical right-handed B form through to the left-handed Z form. However, the biological roles associated with the different structural conformations of DNA are not well understood because of the short lifetime of appearance of each structure and the difficulty in creating a system to demonstrate the DNA local structure. We found that incorporation of 8-methyl-2'-deoxyguanosine (m8G) and 8-methylguanosine (m8rG) into DNA dramatically stabilized the Z form, and facilitated the B-Z transition, even for AT-containing sequences. Developing a Z-stabilizing monomeric unit, the Z stabilizer, allowed us to understand the solution structure of Z-DNA and to reveal the specific 2'β-hydrogen abstraction that gives rise to the Z-form-specific 2'α-hydroxylation of the 5-halouracil-containing Z-form under UV irradiation. We also investigated the photoreaction of 5-halouracil in the A-form, B-form, G-quartet, and protein-induced DNA kinks. Hydrogen abstraction by 2'-deoxyuridin-5-yl generated from 5-halouracil under irradiation was atom specific and highly dependent on the DNA structure.
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