| Project/Area Number |
14207097
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SEKIMIZU Kazuhisa The University of Tokyo, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学系研究科, 教授 (90126095)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Takahiro The University of Tokyo, Graduate School of Pharmaceutical Sciences, Research Associate, 大学院・薬学系研究科, 助手 (00323452)
秋光 信佳 東京大学, 大学院・薬学系研究科, 助手 (40294962)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥45,500,000 (Direct Cost: ¥35,000,000、Indirect Cost: ¥10,500,000)
Fiscal Year 2003: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2002: ¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
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| Keywords | transcription factor / S-II / RNA polymerase II / development / gene knock-out / yeast cells / yeast two hybrid method / erythro differentiation / 遺伝子ノックアウトマウス / イースト2ハイブリッド法 / マウス / 胎生致死 / 酸化ストレス / 酸化型損傷塩基 / 転写忠実度維持 |
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| Research Abstract |
S-II was originally identified as a stimulatory factor of RNA polymerase II in vitro. We have been studying biology of this protein for more than 30 years. Nowadays, S-II is recognized as a transcription elongation factor ubiquitously present in eukaryotic cells. A number of researchers are now studying a role of S-II in eukaryotic transcription. It has been proposed that 5-11 plays an important role on the regulation of transcription in eukaryotic cells. However, there is no direct evidence supporting this notion.
The purpose of this project was to test a hypothesis that. S-II plays a role in oxidative stress response in cells. We also hypothesized that S-II is essential for development. We examined phenotypes of yeast cells and mice whose S-II genes were deleted by homologous recombination technique. We showed that yeast deletion mutant of the S-II gene showed higher sensitivity to oxidative stress. We also demonstrated that fidelity of transcription decreased in the mutant. Oxidative stress may cause oxidization of nucleotides that are substrates for RNA synthesis. Furthermore, embryos of mice deletion mutant of the S-II gene showed lethality at early stage of development. We found that the mutant showed abnormal phenotype in erythro differentiation. These results supports our hypothesis that S-II is important for tolerance to oxidative stress and is essential for development of individual bodies.
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