Theoretical and experimental analysis of the binding efficiency of Ku protein to radiation induced clustered DNA damages
| Project/Area Number |
16K00554
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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 |
Risk sciences of radiation and chemicals
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小池 学 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 重粒子線治療研究部, 主幹研究員(定常) (70280740)
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| 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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | クラスターDNA損傷修復 / DNA二本鎖切断 / Ku / 分子シミュレーション / ライブセルイメージング / クラスターDNA損傷 / DNA修復 / DSB修復 / APサイト / NHEJ |
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| Outline of Final Research Achievements |
Ionizing radiations generate multiple lesions along a single radiation track, that is known as a clustered DNA damage, and those multiple lesions are supposed to develop into DNA double strand breaks (DSBs). In the current project, we constructed models of the clustered DNA damage assembling several DNA lesions and estimated the binding efficiency between damaged DNA and Ku that is a key protein to recognize and bind to the DSB site, using both experimental and theoretical approaches. In addition, we examined the dynamics of Ku in the nucleus of canine cultured cells using the live cell imaging method, and succeeded in observing the accumulation of Ku70 and Ku80, subunits of Ku, at DNA damage sites produced by laser-microirradiation.
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| Academic Significance and Societal Importance of the Research Achievements |
放射線被曝によって生じるDNA損傷は狭い範囲に集中しやすい特徴があり、単独損傷に比べて修復されにくいと言われている。複数の損傷が修復されないまま蓄積すると二本鎖切断(DSB)に発展しやすい。DSBは正常に修復されなければ強力な突然変異原となり細胞死の一因にもなることから、細胞にとって最も重篤な損傷の一つと考えられる。本研究課題を通してDSB修復酵素であるKuが認識・結合しやすい末端形状の特徴を明らかにすることができれば、放射線被曝によるDNA損傷が誘発する生物現象と、細胞内代謝や化学物質への曝露といった他の損傷誘発要因によって生じる現象との違いを明らかにできるのではないかと考えている。
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Report
(4 results)
Research Products
(9 results)
