| Project/Area Number |
15K06826
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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) |
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) |
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 | がん遺伝子 / DNA複製 / DNA損傷 / DNAポリメラーゼ / 損傷乗り越えDNA合成 / 複製ストレス / 発がん遺伝子 / Myc / 損傷乗り越えポリメラーゼ / MUS81 / ポリメラーゼ・イータ / 合成致死 / DNAポリメラーゼeta / エンドヌクレアーゼ / 複製フォーク / DNA複製ストレス / c-Myc遺伝子 / ゲノム不安定性 / Yファミリー・ポリメラーゼ / ポリメラーゼeta(Pol-eta) |
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| Outline of Final Research Achievements |
Growth of neoplastic cells relies on their tolerance to oncogene-induced replication stress (RS). Translesion synthesis (TLS) plays a critical role in cellular tolerance to various types of RS by employing specialized polymerases. Here, we report that Polη, a Y-family TLS polymerase, promotes cellular tolerance to Myc-induced RS. Polη was recruited to Myc-induced RS sites, and Polη depletion enhanced the Myc-induced slowing and 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 (the S-phase specific endonuclease complex), and concomitant depletion of MUS81-EME2 and Polη enhanced RS and cell death in a synergistic manner. Collectively, these results indicate that Polη alleviates the Myc-induced RS, and highlight the possibility of synthetic sick or lethal interaction between Polη and MUS81-EME2 in cells experiencing Myc-induced RS.
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