Study of maintenance DNA methylation based on the structure of DNA methyltransferase
Project/Area Number |
24570153
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Functional biochemistry
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Research Institution | Osaka University |
Principal Investigator |
SUETAKE Isao 大阪大学, たんぱく質研究所, 准教授 (80304054)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | Dnmt / DNA methylation / epigenetics / DNAメチル化 / Dnmt1 |
Outline of Final Research Achievements |
DNA methylation of cytosine is a key epigenetic modification and crucial for normal development of mammals. DNA methylation patterns were maintained by Dnmt1. Mouse Dnmt1 is composed from multiple domains; the replication foci targeting sequence (RFTS), catalytic domain, and so on. From three-dimensional structure of mouse Dnmt1 lacking the N-terminal platform domain, a striking feature that the RFTS plugs the catalytic pocket is observed. Substrate DNA cannot gain access to the catalytic center unless the RFTS is removed from the catalytic pocket. Uhrf1 is reported to be a prerequisite factor. The SRA domain of Uhrf1 specifically recognizes hemi-methylated CpG. In the present study, I have demonstrated that the direct interaction between the SRA of Uhrf1 and Dnmt1 contributes to the removal of the RFTS from the catalytic pocket to allow access of the substrate hemi-methylated DNA to the catalytic center. I elucidated one of the mechanisms to regulate maintenance methylation.
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Report
(4 results)
Research Products
(38 results)
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[Journal Article] NMR Characterization of the Interaction of the Endonuclease Domain of MutL with Divalent Metal Ions and ATP2014
Author(s)
Mizushima R, Kim JK, Suetake I, Tanaka H, Takai T, Kamiya N, Takano Y, Mishima Y, Tajima S, Goto Y, Fukui K, *Lee YH
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Journal Title
PLoS One
Volume: 9
Issue: 6
Pages: e98554-e98554
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Genome engineering of mammalian haploid embryonic stem cells using the Cas9/RNA system2013
Author(s)
Horii T, Morita S, Kimura M, Kobayashi R, Tamura D, Takahashi RU, Kimura H, Suetake I, Ohata H, Okamoto K, Tajima S, Ochiya T, Abe Y, Hatada I
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Journal Title
PeerJ
Volume: 1
Pages: e230-e230
DOI
Related Report
Peer Reviewed
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[Journal Article] Structural basis of the versatile DNA recognition ability of the methyl-CpG binding domain of methyl-CpG binding domain protein 4.2013
Author(s)
Otani, J., Arita, K., Kato, T., Kinoshita, M., Kimura, H., Suetake, I., Tajima, S., Ariyoshi, M., Shirakawa, M.
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Journal Title
J Biol. Chem.
Volume: 288
Issue: 9
Pages: 6351-6362
DOI
Related Report
Peer Reviewed
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[Journal Article] Hinge and chromoshadow of HP1α participate in recognition of K9 methylated histone H3 in nucleosomes.2012
Author(s)
Mishima Y, Watanabe M, Kawakami T, Jayasinghe CD, Otani J, Kikugawa Y, Shirakawa M, Kimura H, Nishimura O, Aimoto S, Tajima S, Suetake I.
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Journal Title
J Mol Biol.
Volume: 425
Issue: 1
Pages: 54-70
DOI
Related Report
Peer Reviewed
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[Presentation] Hinge and chromoshadow of HP1α participate in recognizing K9 methylated histone H3 in nucleosomes2012
Author(s)
Mishima Y, Watanabe M, Kawakami T, Jayasinghe CD, Otani J, Kikugawa Y, Shirakawa M, Kimura H, Nishimura O, Aimoto S, Tajima S, and Suetake I.
Organizer
FASEB (Federation of American Societies for Experimental Biology) Science Reseach Conference. Biological methylation: From DNA and histone to disease
Place of Presentation
the sivertree hotel, snowmass village, Colorado (USA).
Related Report
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[Presentation] Multi-step process of maintenance methylation2012
Author(s)
Tajima, S., Takeshita, K., Suetake, I., and Nakagawa, A
Organizer
FASEB (Federation of American Societies for Experimental Biology) Science Reseach Conference. Biological methylation: From DNA and histone to disease
Place of Presentation
the sivertree hotel, snowmass village, Colorado.(USA)
Related Report
Invited
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