Assessment of genotoxic agents by using recombination-associated protein-deficient cells

Research Project

Project/Area Number	26740026
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Risk sciences of radiation and chemicals
Research Institution	Hiroshima University
Principal Investigator	Suzuki Tetsuya 広島大学, 医歯薬保健学研究院(薬), 助教 (20573950)
Project Period (FY)	2014-04-01 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	DNA二本鎖切断 / 相同組換え / DNAヘリカーゼ / DNAリゾルベース / 相同組換え修復 / 組換え修復
Outline of Final Research Achievements	DNA helicases and DNA resolvases are believed to play important roles in DNA strand break repair. In this study, we established cell lines deficient in a DNA helicase (WRN/RECQL5) or a DNA resolvase (GEN1/SLX4) and examined their cytotoxic sensitivities toward various genotoxic agents. WRN- and RECQL5-deficient cells displayed higher sensitivity to hydroxyurea than wild-type cells. GEN1-deficient cells displayed higher sensitivity to topoisomerase inhibitors than wild-type cells. SLX4-deficient cells exhibited higher sensitivity to alkylating agents. These results suggest that the knockout of each protein have cytotoxic effects on various genotoxic agents and the proteins may play important role for the practical threshold for genotoxicity.