Tumorigenesis by aberrant maintenance DNA methylation
Project/Area Number |
26250027
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Tumor biology
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Research Institution | The University of Tokyo (2016) Nagoya City University (2014-2015) |
Principal Investigator |
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥40,430,000 (Direct Cost: ¥31,100,000、Indirect Cost: ¥9,330,000)
Fiscal Year 2016: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2015: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2014: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
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Keywords | DNAメチル化 / ゲノム不安定性 / DNA複製 / DNAM維持メチル化 / Dnmt1 / ユビキチン化 / ヒストンH3 / DNAメチル化異常 / 発がん / 癌 / 老化 / 分化 |
Outline of Final Research Achievements |
Dnmt1 specifically binds to two mono ubiquitylated histone H3 such as H3K18Ub/K23/Ub, K14Ub/K18Ub, and K14Ub/K23Ub. The crystal structure of the replication foci targeting sequence (RFTS) of Dnmt1 in complex with H3-K18Ub/23Ub reveals striking differences to the previously identified ubiquitin-recognition structures.The binding of H3-K18Ub/23Ub results in spatial rearrangement of two lobes in the RFTS, suggesting the opening of its active site. Actually, incubation of Dnmt1 with H3-K18Ub/23Ub increases its catalytic activity in vitro. DNA hypomethylation by Dnmt1 knockdown results in an aberrant DNA replication program, leading to genomic instability.
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] A combination of genetic and biochemical analyses for the diagnosis of PI3K-AKT-mTOR pathway-associated megalencephaly.2017
Author(s)
Negishi Y, Miya F, Hattori A, Johmura Y, Nakagawa M, Ando N, Hori I, Togawa T, Aoyama K, Ohashi K, Fukumura S, Mizuno S, Umemura A, Kishimoto Y, Okamoto N, Kato M, Tsunoda T, Yamasaki M, Kanemura Y, Kosaki K, Nakanishi M, Saitoh S.
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Journal Title
BMC Med Genet.
Volume: 18
Issue: 1
Pages: 4-4
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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[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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[Journal Article] Mutational analysis of FOXL2 p.C134W and expression of bone morphogenetic protein 2 in Japanese patients with granulosa cell tumor of ovary.2014
Author(s)
Oseto K, Suzumori N, Nishikawa R, Nishikawa H, Arakawa A, Ozaki Y, Asai H, Kawai M, Mizuno K, Takahashi S, Shirai T, Yamada-Namikawa C, Nakanishi M, Kajiyama H, Kikkawa F, Sugiura-Ogasawara M.
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Journal Title
J Obstet Gynaecol Res.
Volume: 40
Issue: 5
Pages: 197-204
DOI
Related Report
Peer Reviewed
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[Journal Article] Mammalian-specific H2A variant, H2ABbd, is Involved in Apoptotic Induction via Activation of NF-κB Signaling Pathway.2014
Author(s)
Goshima T, Shimada M, Sharif J, Matsuo H, Misaki T, Johmura Y, Murata K, Koseki H, Nakanishi M.
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Journal Title
J Biol Chem.
Volume: 未定
Issue: 17
Pages: 11656-66
DOI
Related Report
Peer Reviewed
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