| Project/Area Number |
23501257
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Carcinogenesis
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| Research Institution | Gunma University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ODA Tsukasa 群馬大学, 生体調節研究所, 助教 (10323643)
SEKIMOTO Takayuki 群馬大学, 生体調節研究所, 助教 (20436322)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | DNA複製 / DNA複製ストレス / Y-family polymerase / cyclin E / geminin / ゲノム不安定性 / 前がん病変 / 発がん / Yファミリー・ポリメラーゼ / 発がん遺伝子 / 突然変異 / ゲノム不安定化 |
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| Research Abstract |
In preneoplastic lesions, oncogene-induced replication stress plays a dual role induction of cell senescence/apoptosis and tumor promotion through increased genomic instability. In these processes, oncogene-induced excessive activation of replication origins and consequent rereplication plays a major role. However, little is known about fork progression during rereplication. When rereplication was induced by depletion of geminin, a regulator of origin activation, Pol-eta was recruited to rereplication sites in human cell lines. Similar observations were obtained in cyclin E-induced rereplication in human tumor cells. Furthermore, Pol-eta knockdown suppressed rereplication induced by either geminin depletion or cyclin E expression. Together, our data suggest that Pol-eta participates in oncogene-induced rereplication. These findings provide important mechanistic insights into genomic instability during tumorigenesis.
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