2017 Fiscal Year Final Research Report
H2AX plays a pivotal role in proper chromosome segregation
| Project/Area Number |
15K08280
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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 |
General medical chemistry
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| Research Institution | Yamaguchi University (2017)
Nagoya City University (2015-2016) |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | ヒストン / クロマチン / 染色体分配 / エピジェネティクス / Aurora B |
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| Outline of Final Research Achievements |
Proper deposition and activation of Aurora B at centrosomes is critical for faithful chromosome segregation in mammals. We demonstrate here that Aurora B-mediated phosphorylation of histone H2AX at serine 121 promotes Aurora B autophosphorylation and is essential for proper chromosome segregation. H2AX knockout MEFs as well as knockdown cells showed a severe defect in cell proliferation, due to increased abnormal mitosis. H2AX depletion resulted in a severe defect in activation and deposition of Aurora B at centromeres, due to impaired Haspin-dependent H3-T3 phosphorylation. Wild-type H2AX, but not the S121A mutant, effectively rescued the impaired proliferation of H2AX-depleted cells. Taken together, these results indicate that Aurora B-mediated H2AX phosphorylation at S121 provides a platform for Aurora B auto-activation circuitry at centromeres and thus plays a pivotal role in proper chromosome segregation.
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| Free Research Field |
細胞生物学
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