Analysis of novel mechanism for regulation of DNA replication start
| Project/Area Number |
24390072
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial 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 | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2012: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | HBO1 / DDB2 / ユビキチン / UV / DNA複製 / ATM/ATR / DNA損傷応答 / チェックポイント / ライセンシング / DNAダメージ / DNA損傷修復 |
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| Outline of Final Research Achievements |
HBO1 plays positive regulation for cell proliferation under unperturbed condition, whether there is regulation mechanism of HBO1 under DNA damage is poorly understood. We demonstrated that HBO1 was degraded after DNA damage to suppress cell proliferation. Ser50 and Ser53 of HBO1 were ATM and ATR-dependently phosphorylated after UV treatment. ATM/ATR-dependent phosphorylated HBO1 preferentially interacted with DDB2 and was ubiquitylated by CRL4DDB2. Replacement of endogenous HBO1 to Ser50/53Ala mutants maintained acetylation of histone H3K14 and impaired cell cycle regulation in response to UV. These results indicated that HBO1 is one of the targets by DNA damage checkpoint. These results show that ubiquitin-dependent control of HBO1 protein contributes to cell survival toward UV irradiation.
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Report
(5 results)
Research Products
(14 results)
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[Journal Article] UV Damage-Induced Phosphorylation of HBO1 Triggers CRL4DDB2-Mediated Degradation To Regulate Cell Proliferation.2015
Author(s)
Matsunuma R, Niida H, Ohhata T, Kitagawa K, Sakai S, Uchida C, Shiotani B, Matsumoto M, Nakayama KI, Ogura H, Shiiya N, Kitagawa M.
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Journal Title
Mol Cell Biol.
Volume: 36
Issue: 3
Pages: 394-406
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Involvement of ribonucleotide reductase-M1 in 5-fluorouracil induced DNA damage in esophageal cancer cell lines.2013
Author(s)
Aoki Y, Sakogawa K, Hihara J, Emi M, Hamai Y, Kono K, Shi L, Sun J, Kitao H, Ikura T, Niida H, Nakanishi M, Okada M, Tashiro S.
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Journal Title
Int J Oncol.
Volume: 42(6)
Issue: 6
Pages: 1951-60
DOI
Related Report
Peer Reviewed
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