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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| Project Status |
Completed (Fiscal Year 2017)
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| 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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| 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 / ヒストン修飾 / H2AX |
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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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Report
(4 results)
Research Products
(12 results)
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[Journal Article] The G2 checkpoint inhibitor CBP-93872 increases the sensitivity of colorectal and pancreatic cancer cells to chemotherapy.2017
Author(s)
Iwata T, Uchino T, Koyama A, Johmura Y, Koyama K, Saito T, Ishiguro S, Arikawa T, Komatsu S, Miyachi M, Sano T, Nakanishi M, Shimada M.
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Journal Title
Plos one
Volume: 12
Issue: 5
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Activation of Endogenous Retroviruses in Dnmt1-/- ESCs Involves Disruption of SETDB1-Mediated Repression by NP95 Binding to Hemimethylated DNA.2016
Author(s)
Sharif J, Endo TA, Nakayama M, Karimi MM, Shimada M, Katsuyama K, Goyal P, Brind'Amour J, Sun MA, Sun Z, Ishikura T, Mizutani-Koseki Y, Ohara O, Shinkai Y, Nakanishi M, Xie H, Lorincz MC, Koseki H.
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Journal Title
Cell Stem Cell
Volume: Epub ahead of print
Issue: 1
Pages: 999-999
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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