| Project/Area Number |
17K09157
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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 |
Hygiene and public health
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| Research Institution | Kawasaki Medical School (2019-2020)
Okayama University (2017-2018) |
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Principal Investigator |
Ito Tatsuo 川崎医科大学, 医学部, 講師 (80789123)
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| Co-Investigator(Kenkyū-buntansha) |
長岡 憲次郎 岡山大学, 医歯薬学総合研究科, 助教 (40752374)
江口 依里 福島県立医科大学, 医学部, 講師 (60635118)
荻野 景規 高知大学, 医学部, 特任教授 (70204104)
大内田 守 岡山大学, 医歯薬学総合研究科, 准教授 (80213635)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 悪性中皮腫 / BAP1 / NHEJ / DNA-PKcs / CRISPR/Cas9 / 染色体遺伝子不安定性 / DNA二重鎖切断修復 / in vivo発がん試験 / 社会医学 |
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| Outline of Final Research Achievements |
BRCA1-associated protein 1 (BAP1) is one of the major tumor suppressor genes in malignant pleural mesothelioma. In this study, we clarified the role of BAP1 in nonhomologous end-joining (NHEJ).
RESULTS: We found that inactivation of BAP1 was associated with increased DNA damage in both human mesothelial cells and human malignant mesothelioma cell lines. Furthermore, proteomic analysis identified DNA protein kinases (DNA-PKcs), which function in the NHEJ pathway of DNA repair, as interaction partners of the BAP1 protein complex in MPM and 293T cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、BAP1がDNA-PKとの相互作用を介して二本鎖DNA修復のNHEJ経路に関与していることを示しており、悪性中皮腫のようにBAP1の不活性化が頻繁に見られるがんでは、治療及び、予後診断の標的となりうるDNA修復の脆弱性が明らかになった。
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