| Project/Area Number |
22570178
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
MIZUNO Takeshi 独立行政法人理化学研究所, 今本細胞核機能研究室, 専任研究員 (30281629)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | DNAポリメラーゼα / 染色体複製 / ポリメラーゼα特異的阻害剤 / デヒドロアルテヌシン / 複製工場 / pot1 / 天然変性タンパク質 / 染色体末端 / テロメア / DNAポリメラーゼ / 核内品質管理機構 / 温度感受性変異体 / 核内タンパク質分解 / HSP90 / tsFT20 / noboviocine / DNA複製 / タンパク質分解 / 複製フォーク / ゲノム恒常性 / 細胞ストレス |
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| Research Abstract |
To understand molecular mechanism of mammalian DNA replication, I have focused on mouse DNA polymerase alpha. According to extensive analysis of DNA polymerase alpha,
1) we developed a novel potent inhibitor for mammalian DNA polymerase alpha, from derivatives of dehydroaltenusin. Using this novel inhibitor, we discussed that uncoupling of leading strand synthesis and lagging strand synthesis caused aberrant RPA foci in mammalian nucleus in NIH3T3 cells. 2) Characterization of temperature-sensitive mutant cell line which has mutation in DNA polymerase alpha, suggested novel nuclear protein quality control mechanism to eliminate aberrant proteins from nucleus. In this quality control mechanism involves HSP90 and PA28gamma. 3) Interaction between DNA polymerase alpha and pot1 revealed intrinsically disordered region of DNA polymerase alpha serves as molecular binding site for chromatin binding protein which contains typical OB-fold containing proteins such as RPA, Mcm10, pot1, CST complex.
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