2013 Fiscal Year Final Research Report
Establishment of damage dose-dependent senescence inducible system and its application for understanding molecular basis underlying geriatiric diseases
| Project/Area Number |
24659137
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Nagoya City University |
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Principal Investigator |
NAKANISHI Makoto 名古屋市立大学, 医学(系)研究科(研究院), 教授 (40217774)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 老化 / シグナル伝達 / 発現抑制 |
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| Research Abstract |
Since induction of cellular senescence might be dependent on a number of DNA double strand breaks, we introduced various I-SceI restriction sites in normal human fibroblasts, which is not normally observed in normal human cells, and analysed whether these cells undergo senescence or not. However, during our experimental course, we found that only single DNA double strand break was sufficient for the induction of senescence when the break occurred during G2 phase. p53 activation during G2 resulted in a mitosis skip, leading to a generation of tetraploid G1 cells. This mitosis skip was collaboratively regulated by premature activation of APC-C/Cdh1 through Cdk1 and Cdk2 inhibition by induced p21 and pRb-family pocket protein dependent transcriptional repression of mitotic regulators.
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[Journal Article] Necessary and sufficient role for a mitosis skip in senescence induction2014
Author(s)
Johumra 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: (In press)
Peer Reviewed
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[Journal Article] Mammalian-specific H2A variant, H2ABbd, is Involved in Apoptotic Induction via Activation of NF-κB Signaling Pathway2014
Author(s)
Goshima T1, Shimada M, Sharif J, Matsuo H, Misaki T, Johmura Y, Murata K, Koseki H, Nakanishi M
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Journal Title
DOI
Peer Reviewed
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[Journal Article] Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication2013
Author(s)
Nishiyama A, Yamaguchi L, Sharif J, Johmura Y, Kawamura T, Nakanishi K, Shimamura S, Arita K, Kodama T, Ishikawa F, Koseki H, Nakanishi M
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Journal Title
Nature.
Volume: 502(7470)
Pages: 249-53
DOI
Peer Reviewed
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[Journal Article] Involvement of ribonucleotide reductase-M1 in 5-fluorouracil-induced DNA damage in esophageal cancer cell lines2013
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)
DOI
Peer Reviewed
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[Journal Article] Chk1 phosphorylates the tumour suppressor Mig-6, regulating the activation of EGF signalling2012
Author(s)
Liu N, Matsumoto M, Kitagawa K, Kotake Y, Suzuki S, Shirasawa S, Nakayama KI, Nakanishi M, Niida H, Kitagawa M
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Journal Title
EMBO J.
Volume: 31(10)
Pages: 2365-77
DOI
Peer Reviewed
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[Journal Article] TANK-binding kinase 1 (TBK1) controls cell survival through PAI-2/serpinB2 and transglutaminase 22012
Author(s)
Delhase M, Kim SY, Lee H, Naiki-Ito A, Chen Y, Ahn ER, Murata K, Kim SJ, Lautsch N, Kobayashi KS, Shirai T, Karin M, Nakanishi M
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 109(4)
Pages: E177-86
DOI
Peer Reviewed
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