| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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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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