| Project/Area Number |
12557208
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
ENOMOTO Takemi Tohoku University, Gradu. School of Pharmaceut. Sci., Professor, 大学院・薬学研究科, 教授 (80107383)
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| Co-Investigator(Kenkyū-buntansha) |
HURUICHI Yasuhiro Gene Care Research Institute, Director, 研究所長(研究職)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 2001: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2000: ¥6,500,000 (Direct Cost: ¥6,500,000)
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| Keywords | Bloom syndrome / homologous recobination / targeted integration / BLM / ATM / yeast Sgs1 / RecQL1 / RecQL5 / RecQファミリーヘリカーゼ / targeted-integration / 阻害剤スクリーニング |
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| Research Abstract |
The aim of this study is to identify the proteins involved in the homologous recombination that is suppressed by BLM and to establish a method that enable us to perform targeted integration highly efficiently by inhibiting BLM function. Although we could not succeed to find good inhibitors for BLM, we obtained important information concerning the function of BLM and the recombination that occurs in the absence of BLM.
1. By generating and analyzing double gene knockout DT40 cells, BLM and RAD54, RAD51, ATM, MRE11, RECQL1, or RECQL5, it was indicated that that the majority of increased sister chromatid exchanges (SCEs) in BLM disrupted cells are formed via homologous recombination, and the contribution of ATM and MRE 11 to the SCE is relatively small. In contrast, ATM greatly contributed to the targeted integration the frequency of which was increased by disruption of BLM gene.
2. The analysis using DT 40 cells also indicated that RecQL5 was involved in the targeted integration in BLM gene knockout cells.
3. An analysis of yeast SGS1 (the yeast homologue of BLM) gene disruptants indicated that Sgs1 functions to suppress recombination under normal conditions but functions to induce recombination under damage-inducing conditions probably interacting with topoisomerase III.
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