Structural studies on proteins involved in template switching pathway
Project/Area Number |
16H04755
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Structural biochemistry
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Research Institution | University of Shizuoka |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
原 幸大 静岡県立大学, 薬学部, 講師 (80729343)
菱木 麻美 静岡県立大学, 薬学部, 助教 (60571172)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
|
Keywords | DNA損傷応答 / X線結晶構造解析 / DNA修復 / 構造生物学 / タンパク質 |
Outline of Final Research Achievements |
Template switching (TS), also known as the damage avoidance path-way, in which one newly synthesized strand is utilized as an undamaged template for replication by replicative polymerases, is an error-free process. Several DNA helicases including HLTF and ZRANB3 are crucially engaged in this pathway and these are involved in reversal of the replication fork. HLTF and ZRANB3, might be involved in the early and late stages of the TS, respectively. Also, PARI that is recently identified protein that inhibit homologous recombination thereby stimulating TS. In this study, crystal structures of the HLTF N-terminal domain bound to DNA and PCNA bound to the ZRANB3 peptides have been determined. These structures reveal interactions of these protein complexes and mechanisms of these interactions.
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Academic Significance and Societal Importance of the Research Achievements |
私たちのDNAは毎日様々な要因によって損傷を受けているが、適切な修復機構によって直されている。しかしDNAのコピーが作られるときに損傷が生じるとDNAのコピーが途中で止まってしまい、細胞にとって好ましくない。このような状況を回避する手段の一つがテンプレートスイッチ(TS)である。TSは損傷の無いDNAを使ってコピーを作る。その一方で、TSはがん細胞が抗がん剤抵抗性を獲得する要因の一つである。しがたって、TSのメカニズムを解明することで新たな創薬の手がかりを得ることができる。本研究ではTSを行うためのタンパク質とDNAとの相互作用、タンパク質とタンパク質との相互作用メカニズムをの一端を解明した。
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Report
(4 results)
Research Products
(93 results)
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[Journal Article] Dynamic feature of mitotic arrest deficient 2-like protein 2 (MAD2L2) and structural basis for its interaction with chromosome alignment maintaining phosphoprotein (CAMP)2017
Author(s)
Hara K, Taharazako S, Ikeda M, Fujita H, Mikami Y, Kikuchi S, Hishiki A, Yokoyama H, Ishikawa Y, Kanno S, Tanaka K, Hashimoto H.
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Journal Title
Journal of Biological Chemistry
Volume: 292
Issue: 43
Pages: 17658-17667
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of the first small-molecule inhibitor of the REV7 DNA repair protein interaction.2016
Author(s)
Actis ML, Ambaye ND, Evison BJ, Shao Y, Vanarotti M, Inoue A, McDonald ET, Kikuchi S, Heath R, Hara K, Hashimoto H, Fujii N.
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Journal Title
Bioorg Med Chem
Volume: 24
Issue: 18
Pages: 4339-4346
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis2016
Author(s)
Tsuyoshi Yamamoto, Yuta Tsunematsu, Kodai Hara, Tomohiro Suzuki, Shinji Kishimoto, Hirokazu Kawaguchi, Hiroshi Noguchi, Hiroshi Hashimoto, Yi Tang, Kinya Hotta, & Kenji Watanabe
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Journal Title
Angew Chem Int Ed Engl
Volume: 印刷中
Issue: 21
Pages: 6207-6210
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] The dimerization domain of the hypertrophy-responsive transcription factor GATA4 is a therapeutic target for heart failure2018
Author(s)
Satoshi Shimizu, Kodai Hara, Yoichi Sunagawa, Asami Hishiki, Masafumi Funamoto, Yusuke Miyazaki, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
第82回日本循環器学会学術集会
Related Report
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[Presentation] GATA4 acetylation site is important for development cardiomyocyte hypertrophy2018
Author(s)
Satoshi Shimizu, Kodai Hara, Yoichi Sunagawa, Asami Hishiki, Masafumi Funamoto, Sari Nurmila, Kana Shimizu, Yusuke Miyazaki, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
23rd Annual Scientific Meeting of the International Society of Cardiovascular Pharmacotherapy
Related Report
Int'l Joint Research
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[Presentation] Determination and crystallization of GATA4 dimerization domain2018
Author(s)
Satoshi Shimizu, Kodai Hara, Yoichi Sunagawa, Asami Hishiki, Yusuke Miyazaki, Yasufumi Katanasaka, Masafumi Funamoto, Sari Nurmila, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
IUBMB Focused Meeting on GATA Transcription Factors
Related Report
Int'l Joint Research
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[Presentation] Inhibition of GATA4 Dimerization Suppresses Cardiac Hypertrophic Responses2018
Author(s)
Satoshi Shimizu, Yoichi Sunagawa, Kodai Hara, Asami Hishiki, Yusuke Miyazaki, Yasufumi Katanasaka, Masafumi Funamoto, Nurmila Sari, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
AHA Scientific Session 2018
Related Report
Int'l Joint Research
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[Presentation] Inhibition of GATA4 dimerization is a novel target for heart failure therapy2018
Author(s)
Satoshi Shimizu, Yoichi Sunagawa, Kodai Hara, Asami Hishiki, Yusuke Miyazaki, Yasufumi Katanasaka, Masafumi Funamoto, Nurmila Sari, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
The 4th International Conference on Pharma-Food (ICPF 2018)
Related Report
Int'l Joint Research
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[Presentation] The acetylation site of GATA4 have an important role for GATA4 dimerization and cardiomyocyte hypertrophy2018
Author(s)
Satoshi Shimizu, Yoichi Sunagawa, Kodai Hara, Asami Hishiki, Yusuke Miyazaki, Yasufumi Katanasaka, Masafumi Funamoto, Nurmila Sari, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
第23回 静岡健康・長寿学術フォーラム
Related Report
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[Presentation] Inhibition of GATA4 Dimerization Suppresses Cardiac Hypertrophic Responses2018
Author(s)
Satoshi Shimizu, Yoichi Sunagawa, Kodai Hara, Asami Hishiki, Yusuke Miyazaki, Yasufumi Katanasaka, Masafumi Funamoto, Nurmila Sari, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Hiroshi Hashimoto, Tatsuya Morimoto
Organizer
日本循環器学会第152回東海・第137回北陸合同地方会
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[Book] レファレンス物理化学2017
Author(s)
近藤伸一、米持悦生、山中淳平(編)
Total Pages
350
Publisher
廣川書店
ISBN
9784567223706
Related Report