| Project/Area Number |
18310037
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MIYAGAWA Kiyoshi The University of Tokyo, Graduate School of Medicine, Professor (40200133)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,980,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2006: ¥8,100,000 (Direct Cost: ¥8,100,000)
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| Keywords | DNA damage / damage response / chromosome / DNA replication / radiation |
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| Research Abstract |
It is important to understand cellular phenotypes that respond to spontaneously arising DNA damage without exogenous DNA damage. We have examined the effect of altered homologous recombination function on cell functions from the viewpoint of chromosome instability. Because Rad51B and XRCC3 play a role in homologous recombination in concert with Rad51, we used the human colon cancer cell line in which these genes were knocked out. We have shown that Rad51B prevents the generation of aneuploidy by stabilizing the centrosome. We previously showed that XRCC3 prevents chromosome duplication. Increased Cdt1 stability and increased accumulation of Cdc6 in the nucleus have been assumed to contribute to chromosome duplication in XRCC3 deficient colon cancer cells. This possibility was examined in other human cells. Chromosome duplication due to XRCC3 dysfunction was observed in cancer cells in which Cdt1 is stabilized, whereas it is not obviously observed in normal cells, in which Cdt1 is not stable. Because we previously showed that RPA is associated with XRCC3, the effect of RPA was examined in this system by RNA interference. Reduced levels of EPA prevented chromosome duplication induced by XRCC3 dysfunction, suggesting that EPA mediates the control of chromosome ploidy by XRCC3 in response to spontaneously arising DNA damage.
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