Development of DNA modification enzymes based on sequence-specificity of DNA binding domains and their application for genome editing.
Project/Area Number |
25410171
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Bio-related chemistry
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Nomura Wataru 東京医科歯科大学, 生体材料工学研究所, 准教授 (80463909)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | タンパク質 / メチル化 / 人工酵素 / エピゲノム編集 / 核酸 / ケミカルバイオロジー / 合成生物学 |
Outline of Final Research Achievements |
Improvement of genome editing tools such as CRISPR-Cas9 system leads to the increased demands for other gene modification tools such as DNA recombination and methylation. The split DNA methylase bearing split M.HhaI domains and zinc finger domains show the potential for the highly specific DNA methylation. Structural modelling study suggested that the DNA-split methylase complex could contain steric hindrance in some parts. Thus altered DNA assembly of split methylase on the target gene and several linker mutations were tested to obtain the increased activity in DNA methylation without losing sequence specificity. As the results, the assembly pattern in which ZFPs bind to the different strand on the target DNA showed increased activity in DNA methylation. In addition, the extension of linker length between the domains also affected on the increased activity. Above all, the results give new insights into the assembly of split protein domains especially on the target DNA.
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Report
(4 results)
Research Products
(43 results)
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[Journal Article] Development of a fluoride-responsive amide bond cleavage device that is potentially applicable to a traceable linker2014
Author(s)
J. Yamamoto, N. Maeda, C. Komiya, T. Tanaka, M. Denda, K. Ebisuno, W. Nomura, H. Tamamura, Y. Sato, A. Yamauchi, A. Shigenaga, and A. Otaka
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Journal Title
Tetrahedron
Volume: 70
Issue: 34
Pages: 5122-5127
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Development of the 8-aza-3-bromo-7-hydroxycoumarin-4-ylmethyl group as a new entry of photolabile protecting groups2014
Author(s)
Takano, H., Narumi, T., Ohashi, N., Suzuki, A., Furuta, T., Nomura, W., Tamamura, H.
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Journal Title
Tetrahedron
Volume: XX
Issue: 29
Pages: 4400-4404
DOI
Related Report
Peer Reviewed
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[Journal Article] Development of a traceable linker containing a thiol-responsive amino acid for the enrichment and selective labelling of target proteins2014
Author(s)
J. Yamamoto, M. Denda, N. Maeda, M. Kita, C. Komiya, T. Tanaka, W. Nomura, H. Tamamura, Y. Sato, A. Yamauchi, A. Shigenaga, and A. Otaka
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Journal Title
Org. Biomol. Chem.
Volume: 12
Issue: 23
Pages: 3821-3826
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] A CD4 Mimic as an HIV Entry Inhibitors: Pharmacokinetics2013
Author(s)
Hashimoto, C., Narumi, T., Otsuki, H., Hirota, Y., Arai, H., Yoshimura, K., Harada, S., Ohashi, N., Nomura, W., Miura, T., Igarashi, T., Matsuhita, S., Tamamura, H.
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Journal Title
Bioorg. Med. Chem.
Volume: 21
Issue: 24
Pages: 7884-7889
DOI
Related Report
Peer Reviewed
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[Journal Article] Cell-Permeable Stapled Peptides Based on HIV-1 Integrase Inhibitors Derived from HIV-1 Gene Products.2013
Author(s)
Nomura W, Aikawa H, Ohashi N, Urano E, Metifiot M, Fujino M, Maddali K, Ozaki T, Nozue A, Narumi T, Hashimoto C, Tanaka T, Pommier Y, Yamamoto N, Komano JA, Murakami T, Tamamura H.
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Journal Title
ACS Chem. Biol.
Volume: 8
Issue: 10
Pages: 2235-2244
DOI
Related Report
Peer Reviewed
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[Book] Peptide Science 20122013
Author(s)
Masuda A, Nomura W, Tamamura H.
Total Pages
419
Publisher
Kazuhisa Sugimura (Ed.), The Japanese Peptide Society, Osaka
Related Report
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[Book] Peptide Science 20122013
Author(s)
Hashimoto C, Nomura W, Komano JA, Tamamura H.
Total Pages
419
Publisher
Kazuhisa Sugimura (Ed.), The Japanese Peptide Society, Osaka
Related Report
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[Book] Peptide Science 20122013
Author(s)
Nomura W, Narumi T, Aikawa H, Tamamura H.
Total Pages
419
Publisher
Kazuhisa Sugimura (Ed.), The Japanese Peptide Society, Osaka
Related Report
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