The mechanism of nucleosome structure regulated by G-quadruplex
| Project/Area Number |
17K05930
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Bio-related chemistry
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| Research Institution | Shizuoka University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | グアニン四重鎖 / ヌクレオソーム / テロメア / ヒストン修飾 / RGG領域 / DNA構造 / DNA結合タンパク質 / エピジェネティクス / 核酸結合タンパク質 / ヘテロクロマチン |
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| Outline of Final Research Achievements |
G-quadruplex (G4) binding protein, TLS/FUS, led to trimethylation of histone H4 at lysine 20 at the heterochromatin of telomeres and downregulation of transcription of telomeric repeat-containing RNA. To investigate the effect of structure of the arginine－glycine－glycine repeat (RGG) domain in TLS/FUS for G4 binding, we analyzed the G4 binding activities of proteins purified in a buffer with high concentrations of urea and KCl to disrupt the β-spiral structure of RGG domain. It reveals that the G4-specific binding abilities of TLS/FUS require β-spiral structure formation of RGG domain. Furthermore, we investigated the effect of the RNA recognition motif (RRM) and RGG domain of nucleolin on G4 binding and formation. Our findings indicate that Phe in RGG domain is responsible for G4 binding and folding. Moreover, RRM potentially binds to a guanine-rich single strand and folds the G4 with a 5′-terminal and 3′-terminal single strand containing guanine.
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝情報を有するDNAやRNAは、単純な１本鎖や典型的な右巻き二本鎖構造だけでなく、細胞内でさまざまな局所構造を形成している。特に、染色体末端構造のテロメアや特定の遺伝子のグアニン塩基が豊富なDNAは、グアニン四重鎖構造を形成して、現代の高齢化社会で問題になっているガンや神経性疾患に関わることが知られている。本研究では、このような疾患に関わっているグアニン四重鎖に結合するタンパク質の機能と構造的特徴、さらにグアニン四重鎖認識機構を明らかにした。これらの結果は、グアニン四重鎖が関わる疾患機構の解明につながるだけでなく、グアニン四重鎖構造を標的とする薬剤の開発に大きく貢献できると考えられる。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Isolation and structure determination of a new cytotoxic peptide, curacozole, from Streptomyces curacoi based on genome mining.2019
Author(s)
Kaweewan, I., Komaki, H., Hemmi, H., Hoshino, K., Hosaka, T., Isokawa, G., Oyoshi, T., and Kodani, S.
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Journal Title
J Antibiot
Volume: 72
Issue: 1
Pages: 1-7
DOI
Related Report
Peer Reviewed
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[Journal Article] Multiplicity in Long Noncoding RNA Biomedical Sciences2018
Author(s)
3.R. Kurokawa, R. Komiya, T. Oyoshi, Y. Matsuno, H. Tani, M. Katahira, K. Hitachi, Y. Iwashita, T. Yamashita, K. Kondo, R. Yoneda, Y. Yamaoki, N. Ueda, T. Mashima, N. Kobayashi, T. Nagata, A. Kiyoishi, M. Miyake, F. Kano, M. Murata1, N. Hamad, K. Sasaki, N. Shoji
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Journal Title
Biomedical Sciences
Volume: 4
Issue: 2
Pages: 18-23
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Bcl-XL-binding helical peptides possessing D-Ala residues at their C-termini with the advantage of long-lasting intracellular stabilities.2017
Author(s)
Nogami, K., Tokumaru, H., Isokawa, G., Oyoshi, T., Fujimoto, K., and Inouye, M
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Journal Title
ChemComm
Volume: 53
Issue: 89
Pages: 12104-12107
DOI
Related Report
Peer Reviewed
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