2018 Fiscal Year Final Research Report
Mechanisms of 53BP1 binding to chromatin in apoptotic cells
| Project/Area Number |
15K12210
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
砂谷 優実 金沢医科大学, 医学部, 講師 (70581057)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Keywords | アポトーシス |
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| Outline of Final Research Achievements |
DNA repair protein 53BP1 accumulates at DNA double-strand break (DSB) sites through binding to di-methylated histone H4 (H4K20me2). JMJD2A and L3MBTL1 also bind H4K20me2 and prevent 53BP1 from binding to H4K20me2. JMJD2A is degraded by the proteasome and L3MBTL1 is released from H4K20me2, following the DNA damage in an E3 ubiquitin ligases RNF8 and RNF168 dependent manner. We found that 53BP1 binds histone H4 after induction of apoptosis triggered by non-DNA damaging apoptosis-inducer staurosporine. After apoptosis induction, JMJD2A was degraded in a caspase-dependent manner, and L3MBTL1 altered its localization from the nucleus to the cytoplasm. These data suggest that there are apoptosis-specific mechanisms to unmask the 53BP1 binding site of histone H4.
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| Free Research Field |
細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
アポトーシス細胞においてクロマチンが細胞表層に露出することは、1994年にすでに見出されているが、核から細胞表層へ移動するメカニズムは全く不明である。一方、代表的自己免疫疾患であるSLEは、クロマチンの構成成分であるDNAやヒストンなどに対する自己抗体の出現がその原因であると考えられている。本研究は、SLEの発症機序の解明に貢献することが期待される。
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