| Project/Area Number |
09672236
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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 |
Biological pharmacy
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| Research Institution | Okayama University |
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Principal Investigator |
MIZUSHIMA Tohru Fac.of Pharm.Sci.Okayama University, Associate Prof., 薬学部, 助教授 (00264060)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | DNA replication / Cancer / anti-cancer drug / ATPase / DnaA蛋白 / ATP |
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| Research Abstract |
Re-replication of DNA from a newly replicated origin is normally suppressed so that coupling of DNA replication with cell division proceeds in an orderly manner. However, the molecular mechanisms for suppression remains unknown, even in prokaryotic cells. In my previous research, I demonstrated that the intrinsic ATPase activity of DnaA protein, the initiation factor for ANA replication in Escherichia coli cells, play a major role in the suppression of
re-replication by inactivating the DnaA function. I also found a stimulation factor for the DnaA ATPase activity and showed that the factor was activated only after the initiation of DNA replication. Based on these results, I proposed a new model for the suppression of re-initiation in Escherichia coli cells. In details, we constructed mutant DnaA protein whose ATPase activity is specifically decreased and showed that induction of a mutated DnaA protein caused over-initiation of chromosomal DNA replication in cells, resulting in a dominant lethal phenotype. These observations suggest that the intrinsic ATPase activity of DnaA protein is involved in the suppression of re-initiation from newly replicated origin in cells
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