2016 Fiscal Year Final Research Report
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 |
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| Research Field |
Tumor therapeutics
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| Research Institution | Gunma University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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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 |
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| 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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| Free Research Field |
細胞生物学
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