Transform the antibodies against DNA lesions into the repair-enhancing reagents of them

• Project/Area Number: 16H02958
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Nara Medical University
• Principal Investigator: MORI Toshio 奈良県立医科大学, 医学部, 特任教授 (10115280)
• Co-Investigator(Kenkyū-buntansha): 杉浦 重樹 奈良県立医科大学, 医学部, 教育教授 (40179130) ; 織田 昌幸 京都府立大学, 生命環境科学研究科, 准教授 (20318231)
• Research Collaborator: IWAMOTO Takaaki ; HIGASHI Nobutake
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000); Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: 紫外線 / DNA修復 / シクロブタン型二量体(CPD) / CPD特異抗体 / 修復亢進 / 損傷修復試薬 / シクロブタン型二量体 / 損傷除去修復薬

Outline of Final Research Achievements

Too much exposure to sunlight produces DNA damage including cyclobutane pyrimidine dimers (CPDs) at exposed skin areas and causes harmful effects including skin cancers. This suggests that quick removal of CPDs from cellular DNA may prevent from such harmful effects. In this study, we examined whether the antibodies against CPD which was bound to restriction enzymes (Fab-X) can increase UV resistance in human cells by stimulating repair efficiency of CPDs. Indeed, we found that Fab-X-expressing human cells showed higher UV survival than control cells, which was related with higher efficiency of CPD repair from genomic DNA. These findings indicate that we can transform the antibodies against DNA lesions into the repair-enhancing reagents of them.

Academic Significance and Societal Importance of the Research Achievements

私達は太陽紫外線で最も多く形成されるDNA損傷(CPD)に特異的なモノクローナル抗体を作製し、同損傷を簡易に定量したり可視化できる貴重な研究ツールとして育てた後、世界の研究者に利用機会を提供してきた。本研究により、CPD特異抗体断片にDNA切断酵素を結合することで、CPDの細胞内での修復を増強できることが判明し、さらに健康面での社会的貢献の可能性があることがわかった。このように、DNA損傷特異抗体を損傷修復試薬に進化させることに成功した。