| Project/Area Number |
09307003
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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 |
General medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OKAYAMA Hiroto Graduate School of Medicine, The University of Tokyo, Professor, 大学院・医学系研究科, 教授 (40111950)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Koichi Graduate School of Medicine, The University of Tokyo, Associate, 大学院・医学系研究科, 助手 (90282615)
JINNO Shigeki Graduate School of Medicine, The University of Tokyo, Associate, 大学院・医学系研究科, 助手 (10251224)
NAGATA Akihisa Graduate School of Medicine, The University of Tokyo, Lecture, 大学院・医学系研究科, 講師 (50155933)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥34,000,000 (Direct Cost: ¥34,000,000)
Fiscal Year 1999: ¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 1998: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1997: ¥17,600,000 (Direct Cost: ¥17,600,000)
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| Keywords | Cell cycle control / fission yeast / cyclin / WD repeat protein / sister chromatid cohesion / Cdk6 / anchorage-independent growth / RNA binding protein / 分化制御 / 二重鎖切断修復 / S期 / 造血細胞 / polη / rad22 / RPA / S期開始 / ORC / MCM / ストレス適応 / DNA複製 |
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| Research Abstract |
Cell cycle control is one of the most complicated cellular regulatory systems and determined the timing and progression of cell proliferation, arrest and differentiation in response to external conditions. Our goal is to understand the entire outline of this regulatory system. To this end, we have been studying rodent fibroblasts and fission yeast as model organisms. In this term, we have mode the following progresses.
1. We have isolated two novel factors that control the cell cycle and differentiation stars. One is a new cyclin and the other a WD repeat protein that controls degradation of B-type cyclin.
2. We have identified two new factors that are essential for the establishment and maintenance of sister chromatid cohesion. One is a protein fused with polη that is required for post-replication repair, and the other a factor required for stability of sister chromatid cohesion and for inhibition of undesired chromatid cohesion.
3. Cdk6-D3 complex among the other D cyclin- kinase combinations is able to evade inhibition by CKls and to control cell's growth competence.
4. Oncogenic stimulation recruits Cdk6 in a critical step of the cell cycle start, via a mechanism seemingly unrelated to the regulation of its activity or subcellular localization. Given that hematopoietic cells employ predominantly Cdk6 for the cell cycle start and perform anchorage-independent growth by nature, this finding raises the possibility that the anchorage-independent cell cycle start induced by oncogenic transformation is elicited by a mechanism similar to the one employed for hematopoietic cell proliferation.
5. We have isolated a human homologue of a fission yeast differentiation regulation. As anticipated, overexpression of this gene blocks magakaryotic and erythroid differentiation of a human leukemia cell.
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