Aurora-A controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis
Use this link to cite this item : https://ir.lib.hiroshima-u.ac.jp/00036273
ID | 36273 |
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title alternative | Aurora-A は細胞分裂期においてgeminin を安定化することで複製前複合体形成やDNA複製を制御する
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creator |
Tsunematsu, Takaaki
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NDC |
Medical sciences
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abstract | Geminin, an essential factor for DNA replication, directly binds to the licensing factor Cdt1 and inhibits pre-replicative complex (pre-RC) formation to prevent re-replication. In G1, geminin levels are controlled by the anaphase-promoting complex/cyclosome ubiquitin ligase complex (APC/C), which targets geminin for proteasomal degradation to allow pre-RC formation. Conversely, from S to G2, geminin is stabilized thanks to APC/C inhibition to ensure inhibition of pre-RC formation. However, mitotic regulation of geminin has hitherto not been described. Here we show that Aurora-A phosphorylates geminin on Thr25 during M phase, and this event induces geminin stabilization by preventing its APC/C-mediated degradation during mitosis. In turn, stabilized geminin inhibits SCFSkp2-mediated degradation of Cdt1 to ensure pre-RC formation in the ensuing S phase. The Aurora-A-geminin-Cdt1 axis therefore represents a critical regulator of proper DNA replication.
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date of created | 2014-11-21
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language |
eng
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nii type |
Thesis or Dissertation
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HU type |
Doctoral Theses
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DCMI type | text
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format | application/pdf
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text version | ETD
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rights | Copyright(c) by Author
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relation references | Takaaki Tsunematsu, Yoshihiro Takihara, Naozumi Ishimaru, Michele Pagano, Takashi Takata & Yasusei Kudo; Aurora-A controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis; Nature Communications Volume 4, Article number 1885 (doi: 10.1038/ncomms2859)
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relation references URL | http://dx.doi.org/10.1038/ncomms2859
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grantid | 甲第6249号
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degreeGrantor | 広島大学(Hiroshima University)
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degreename Ja | 博士(歯学)
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degreename En | Philosophy in Dental Science
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degreelevel | doctoral
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date of granted | 2013-09-25
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department |
Graduate School of Biomedical Science
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