Understanding mechanism of genome instability in hereditary breast cancer induced by telomere dysfunction
| Project/Area Number |
17K08649
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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 |
Pathological medical chemistry
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| Research Institution | Gunma University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | テロメア / 染色体不安定化 / DNA損傷反応 / 細胞周期 / 乳癌 / 遺伝性乳癌 / 染色体末端融合 / DNA損傷応答 / ゲノム不安定化 / ユビキチン化 / 遺伝性乳ガン |
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| Outline of Final Research Achievements |
Breast cancer is currently the most common cancer in women, with hereditary breast cancer accounting for about 10% of the cases. Mutations in the BRCA1 gene, one of the major causative genes in hereditary breast cancer, cause genome instability. Telomeres are localized at the ends of chromosomes to play an important role in genome stabilization. In this study, we focused on telomere function to elucidate the mechanism of genome instability caused by BRCA1 abnormalities.
This study reveals a detailed molecular mechanism by which the BRCA1 complex regulates the ubiquitination of chromatin in the telomere region and represses chromosome end fusion during telomere dysfunction, which leads a genome instability.
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝性乳癌は乳癌の中でも治療に難渋するトリプルネガティブ乳癌に含まれ予後不良であり、BRCA 遺伝子に変異が存在すると70%以上という高率で遺伝性乳癌を発症することから、遺伝性乳癌の病態解明は喫緊の課題の一つである。テロメアによる染色体末端融合は、癌で高率で見られるゲノム不安定化を引き起こす原因であり、本研究で明らかになったBRCA1 複合体による染色体末端融合の分子機構に関する知見は、遺伝性乳癌の病態理解と分子標的治療法の開発につながる。
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Report
(4 results)
Research Products
(14 results)
