Molecular characterization of cell fate determination in the DNA damage response
| Project/Area Number |
26860195
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | Nagoya City University |
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Principal Investigator |
JOHMURA Yoshikazu 名古屋市立大学, 医学(系)研究科(研究院), 助教 (40616322)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 老化 / がん / DNA損傷 / 細胞周期 / p53 |
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| Outline of Final Research Achievements |
DNA damage response is known to induce senescence as well as transient cell cycle arrest and apoptosis, but molecular mechanisms of how cells determine whether or not to undergo senescence are largely unknown. This study show that suppression of DNA repair pathways extends the duration of Chk1-dependent G2 checkpoint activation and sensitizes cells tosenescence through enhancement of mitosis skipping. Extension of G2 checkpoint activation by introduction of the TopBP1 activation domain sensitizes cells to senescence. Importantly, fibroblasts from progeroid syndromes tested shows a strong correlation between a drastic extension of G2 checkpoint activation and an increase in the susceptibility to senescence, suggesting that extension of G2 checkpoint activation caused by defective DNA repair is critical for senescence
predisposition in progeroid syndrome patients. These results indicate that the duration of Chk1-dependent G2 checkpoint directs cells to senescence.
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Report
(3 results)
Research Products
(13 results)
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[Journal Article] SCF(Fbxo22)-KDM4A targets methylated p53 for degradation and regulates senescence.2016
Author(s)
Johmura Y, Sun J, Kitagawa K, Nakanishi K, Kuno T, Naiki-Ito A, Sawada Y, Miyamoto T, Okabe A, Aburatani H, Li S-F, Miyoshi I, Takahashi S, Kitagawa M, Nakanishi M.
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Journal Title
Nat. Commun.
Volume: 7
Issue: 1
Pages: 10574-10574
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Necessary and sufficient role for a mitosis skip in senescence induction.2014
Author(s)
Johmura Y, Shimada M, Misaki T, Naiki-Ito A, Miyoshi H, Motoyama N, Ohtani N, Hara E, Nakamura M, Morita A, Takahashi S, Nakanishi M.
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Journal Title
Mol.Cell
Volume: 55
Issue: 1
Pages: 73-84
DOI
Related Report
Peer Reviewed
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