2020 Fiscal Year Final Research Report
The significance and the molecular mechanism of neocentromere formation at DSB sites
| Project/Area Number |
16K21747
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| Research Category |
Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Molecular biology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2018 – 2020
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| Keywords | セントロメア / ヒストン / 染色体安定性 / DNA損傷 / DNA二重鎖切断 / 放射線感受性 / クロマチン |
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| Outline of Final Research Achievements |
We aimed to define the role of centromere protein A (CENP-A), a histone H3 variant, as a key mediator of this crosstalk. CENP-A is a constituent of the centromere-specific chromatin essential for the assembly of the kinetochore, a proteinaceous structure that provides the connection between chromosomes and spindle microtubules. CENP-A plays a crucial role in centromere identity and kinetochore assembly. Interestingly, CENP-A also localizes to DNA double-strand breaks (DSBs) but not at other DNA lesions. We found that CENP-A depleted cells were highly sensitive to ionizing irradiation, but over-expression of CENP-A reduced radiosensitivity. We identified several novel proteins that associate with CENP-A specifically when DSBs occur. We also found BUB1, a spindle checkpoint component, is present at DSBs. Our results suggest the role of CENP-A in the activation of the spindle checkpoint in response to failed DNA damage repair.
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| Academic Significance and Societal Importance of the Research Achievements |
環境因子である放射線、重金属、大気汚染と変異誘導化合物の細胞への曝露はDNA二重鎖切断や他のDNA欠損を引き起こす。このような環境によって引き起こされたDNA欠損は保存されたDNA損傷反応機構によって修復される。DNA損傷反応機構に問題があると、DNAは修復されず、ガンや発達障害などの重篤な健康障害が引き起こされる。DNA二重鎖切断時におけるCENP-Aのスピンドルチェックポイントの活性化をする役割を示唆する我々の結果はこの分子機構の解明に貢献する。
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| Free Research Field |
細胞生物学
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