Analysis of a ATM-RNF8 dependent NHEJ pathway in tumor quiescent cells following heavy ion irradiation.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26740023
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: Nakajima Nakako 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 放射線障害治療研究部, 研究員(任常) (50402863)
• Research Collaborator: Yajima Hirohiko 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・放射線障害治療研究部, 主任研究員 (30261895) ; Shibata Atsushi 群馬大学, 先端科学研究指導者育成ユニット, 助教 (30707633)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 放射線 / 重粒子線 / DNA修復

Outline of Final Research Achievements

Heavy ions induce multiple closely localised double strand break sites (Clustered DSBs). The clustered DSBs are repaired dependently by E3 ubiquitin ligase RNF8. RNF8 is known as a DNA repair factor within the heterochromatin (HC) region. We found that HC-building factor siKAP1 did not affect the repair defect in RNF8 knockdown cells post Fe ions irradiation. This suggests that RNF8 is required for clustered DSBs repair following heavy ion irradiation not only in HC-regions but also in euchromatin regions. It is also known that RNF8 recruits 53BP1 and BRCA1 to DSB sites. The repair of clustered DSBs in 53BP1 knockdown cells were impaired to similar levels as the defect in RNF8 knockdown cells, whereas no repair defect was observed in BRCA1 knockdown cells. Taken together, clustered DSBs induced by heavy ions are repaired by RNF8-53BP1 dependent pathway.

Free Research Field

生物学