Structure Biology Study on Effects of Hyperthermia on Ku: Evolution From DNA Damage Repair to Protein Damage Repair
| Project/Area Number |
17K20042
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Environmental analyses and evaluation and related fields
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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| Keywords | 温熱 / 放射線 / DNA修復 / Ku / 円二色性分光 / タンパク質変性 / 蛋白質 / 核酸 / 生体分子 / 癌 |
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| Outline of Final Research Achievements |
We clarified the effects of heat treatment on the response of DNA-PK to DNA double-strand break (DSB) by measuring XRCC4 phosphorylation at Ser320 after irradiation. Next, we found that heat treatment reduced in the solubility of DNA ligase IV, which is involved in DSB repair through non-homologous end joining, and the abundance of BRCA2, which is involved in DSB repair through homologous recombination. Finally, we analyzed the secondary structures of XRCC4, its family member XLF and PAXX and p53 and the effects of heat therein by vacuum-ultraviolet circular dichroism (VUVCD) spectroscopy. We found the heat-induced alteration in the content of alpha-helix, beta-sheet, turn and random coil in p53 and also succeeded in obtaining the secondary structure of full-length XRCC4.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、放射線によって生じるさまざまなDNA損傷の中で最も致命的と考えられるDNA二重鎖切断修復に関わるタンパク質に対する温熱の作用の一端を明らかにすることができた。今後、さらに研究を続けて行くことで、タンパク質の最も基本的で普遍的な性質の一つである熱による変性や失活の原理や、変性、失活からの防護、回復のメカニズムを明らかにできることが期待される。また、温熱と放射線の併用は臨床的にもがん治療に応用されており、本研究で得られた知見はがん治療の向上にも貢献できることが期待される。
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Report
(4 results)
Research Products
(28 results)
