The recruitment mechanism of HIV-1 integrase to DNA double-strands break sites

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860313
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: National Center for Global Health and Medicine
• 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)
• 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
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: HIV-1 / DSB / Vpr / Integrase

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.

Free Research Field

分子生物学、ウィルス学、放射線生物学