| Project/Area Number |
18K08340
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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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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 脱ユビキチン化 / USP10 / DNA修復 / 相同組み換え修復 / DNA-PKcs / PP6 / 造血幹細胞 / 相同組換え修復 / 脱ユビキチン化酵素 |
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| Outline of Final Research Achievements |
USP10 is an essential deubiquitinase for haematopoietic stem cells (HSCs) maintenance. Since HSCs maintenance relies on proper DNA damage response (DDR), we investigated whether USP10 is involved in DDR. USP10 KO cells showed impaired DNA double strand break (DSB) repair, which is attributed to impaired homologous recombination (HR) repair. In USP10 KO cells, DNA-PKcs is hyperactivated, and inhibition of DNA-PKcs restored the DSB repair. Thus, USP10 properly regulates DNA-PKcs activity after DSB, contributing to HR repair and HSCs maintenance.
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| Academic Significance and Societal Importance of the Research Achievements |
USP10はDNA-PKの活性制御を行い、DSBのHRによる修復を促進しているという新しい知見を得た。USP10はこの作用によりHSCの維持に寄与していることが示唆された。この結果からUSP10は原因不明の貧血の原因遺伝子である可能性も考えられる。さらにUSP10阻害剤はがんに対する抗がん剤や放射線治療の効果を高めることが期待される。
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