The recruitment mechanism of HIV-1 integrase to DNA double-strands break sites
| Project/Area Number |
26860313
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Virology
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
IIJIMA KENTA 国立研究開発法人国立国際医療研究センター, その他部局等, その他 (20565626)
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| Research Collaborator |
KOBAYASHI Junya 京都大学 放射線生物研究センター, ゲノム動態研究部門, 准教授
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | HIV-1 / DSB / Vpr / Integrase / DNA二重鎖切断 / integrase |
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| Outline of Final Research Achievements |
We have investigated the integration modes of HIV-1 DNA to the artificially induced DSB site through IN-activity independent mechanism. In this study, we notably found the rapid recruitment of two viral proteins (IN and “A”) to the micro-irradiation induced DSB tracks. Surprisingly, the accumulation of IN at the DSB tracks was completely depends on the function of “A”. The analysis using DSB-signaling inhibitors show that the recruitment of “A” to DSB site is independent of ATM and DNA-PKcs activities. We found the DSB sensor protein “B” is required for the recruitment of “A”, and physically interacts with “A”. Along with these data, we found the suppressive role of “A” in one of the cellular DSB repair pathway, NHEJ. Additionally, “A” deficient virus show larger deletions of proviral DNA ends at the DSB /proviral DNA junction, suggesting the requirement of “A” for the intact viral DNA integration at DSB site.
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Report
(3 results)
Research Products
(1 results)
