2012 Fiscal Year Final Research Report
Molecular mechanism of assembly and control of mammalian replication factories
| 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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| 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 |
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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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[Book] Effect of a specific mammalian DNA polymerase α inhibitor, dehydroaltenusin, on DNA replication in cultured cells. pp67-111, DNA Replication and Mutation, Raymond P. Leitner (Ed.) ISBN 978-1-61324-490-62011
Author(s)
Mizuno, T., Kuriyama, I., Takemura, M., Sakaguchi, K., Sugawara, F., Yoshida, H., Mizushina, Y.
Publisher
Nova publisher
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