Analyses of the mechanisms for DNA G-quadruplex resolution as a molecular basis of the treatment of breast and ovarian cancer.
| Project/Area Number |
17H03585
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
Ohta Tomohiko 聖マリアンナ医科大学, 医学研究科, 教授 (60233136)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | 乳癌 / 卵巣癌 / 相同組換修復 / グアニン4重鎖 / G4安定化剤 |
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| Outline of Final Research Achievements |
We investigated mechanisms regulating a secondary DNA structure G-quadruplex (G4) to clarify the significance of G4 stabilizer in cancer treatments. We discovered an essential role of HERC2 in G4 resolution by mediating interaction between single-strand DNA binding protein RPA and DNA helicases BLM and WRN. HERC2 was also required for phosphorylation and ubiquitination of RPA2. This mechanism is critical because G4 accumulation as a result of HERC2 deficiency may provide a therapeutic target for G4 stabilizers.
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| Academic Significance and Societal Importance of the Research Achievements |
乳がんや卵巣がんの中で特に予後の悪いがんの一部は、DNAの修復機能に異常があることがわかっており、これを標的とした治療が有効である。しかし、この治療法における耐性の獲得が問題となっている。本研究により、そのようながんの弱点としてDNAの二次構造であるグアニン四重鎖(G4)が蓄積するメカニズムの1つが解明された。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] HERC2 facilitates BLM and WRN helicase complex interaction with RPA to suppress G-quadruplex DNA.2018
Author(s)
Wu W, Rokutanda N, Takeuchi J, Lai Y, Maruyama R, Togashi Y, Nishikawa H, Arai N, Miyoshi Y,Suzuki N, Saeki Y, Tanaka K, Ohta T.
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Journal Title
Cancer Res.
Volume: 78
Issue: 22
Pages: 6371-6385
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Fbxo22-mediated KDM4B degradation determines selective estrogen receptor modulator activity in breast cancer.2018
Author(s)
Johmura Y, Maeda I, Suzuki N, Wu W, Goda A,Morita M, Yamaguchi K, Yamamoto M, Nagasawa S, Kojima Y, Tsugawa K, Inoue N, Miyoshi Y, Osako T Akiyama F, Maruyama R, Inoue JI, Fukukawa Y, Ohta T, Nkanishi M.
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Journal Title
J Clin Invest.
Volume: 128
Issue: 12
Pages: 5603-5619
DOI
Related Report
Peer Reviewed / Open Access
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