Development of a therapeutic foundation for c-Myc overexpressed cancer by depletion of Y-family DNA polymerase
Project/Area Number |
15K18438
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Tumor therapeutics
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Research Institution | Gunma University |
Principal Investigator |
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Project Period (FY) |
2015-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | Y-family DNAポリメラーゼ / c-Myc / 複製ストレス / Polη / DNA fiber法 / MUS81-EME2 / がん遺伝子誘導性複製ストレス / c-MYC / y-family polymerase |
Outline of Final Research Achievements |
Oncogene-induced replication stress is a major source of DNA damage and genomic instability during tumor development. Thus, understanding of cellular replication stress response mechanisms provides potential therapeutic targets for cancer treatment. This time, we revealed that depletion of Polη, a member of Y-family DNA polymerase, promotes c-Myc induced replication stress. We also show that in the absence of Polη, c-Myc-induced DNA double strand breaks formation depended on MUS81-EME2, the S-phase specific endonuclease complex. We further demonstrate that concomitant depletion of MUS81-EME2 and Polη enhanced replication stress and cell death in a synergistic manner. The present work highlights the possibility of a synthetic sick or lethal interaction between Polη and MUS81-EME2 that can be exploited for c-Myc overexpressed cancer treatment.
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Report
(3 results)
Research Products
(10 results)