| Project/Area Number |
15K06825
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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 |
Tumor biology
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| Research Institution | Gunma University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
YAMASHITA Takayuki 群馬大学, 生体調節研究所, 教授 (10166671)
ODA Tsukasa 群馬大学, 生体調節研究所, 助教 (10323643)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 発がん性複製ストレス / Y-familyポリメラーゼ / Polymerase η / Mus81 and EME2 / 合成致死 / c-Myc / Y-family Polymerase / Mus81-EME2 / synthetic lethality / MUS81-EME2 / y-familyポリメラーゼ / 発がんシグナル / 複製ストレス / がん遺伝子 |
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| Outline of Final Research Achievements |
Growth of cancer cells relies on their tolerance of oncogene-induced replication stress (RS). Translesion synthesis (TLS) plays an essential role in cellular tolerance of various types of RS. However, limited information is available about the role of TLS polymerases in oncogene-induced RS.
Polη, a Y-family TLS polymerase, promotes cellular tolerance of Myc-induced RS. Polη was recruited to Myc-induced RS sites, and Polη depletion enhanced the Myc-induced stalling of replication forks and the subsequent generation of double-strand breaks (DSBs). In the absence of Polη, Myc-induced DSB formation depended on MUS81-EME2, and concomitant depletion of MUS81-EME2 and Polη enhanced RS and cell death in a synergistic manner. Collectively, these results indicate that Polη facilitates fork progression during Myc-induced RS. Additionally, the present study highlights the possibility of a synthetic lethal interaction between Polη and MUS81-EME2 in cells experiencing Myc-induced RS.
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