Structural study of maintenance methylation by Dnmt1

2013 Fiscal Year Final Research Report

• Project/Area Number: 23770145
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Osaka University
• Principal Investigator: TAKESHITA Kohei 大阪大学, たんぱく質研究所, 招へい研究員 (80346808)
• Project Period (FY): 2011 – 2013
• Keywords: DNAメチルトランスフェラーゼ１ / X線結晶構造解析 / エピジェネティクス

Research Abstract

The methylated cytosine in genome is epigenetic regulation of gene expression. After the end of DNA replication, newly DNA double strand chain has become hemimethylated state, these cytosine bases in daughter chain is undermodification. Dnmt1 modifies hemimethylated DNA to complete methylated DNA, then Dnmt1 maintain methylated cytosine pattern in genome. In the research project, we aimed to reveal the molecular mechanism of the maintenance methylation by Dnmt1. we succeeded to prepare Dnmt1 and substrate complex protein. Also, we succeeded to determine a full-length Dnmt1 at 3.8 angstrom.

Research Products

• [Journal Article] The DNA methyltransferase Dnmt1 directly interacts with the SET and RING finger-associated (SRA) domain of the multifunctional protein Uhrf1 to facilitate accession of the catalytic center to hemi-methylated DNA (2014)
  • Author(s): Berkyurek AC, Suetake I, Arita K, Takeshita K, Nakagawa A, Shirakawa M, Tajima S
  • Journal Title: J Biol Chem Volume: 289(1) Pages: 379-86
  • DOI: 10.1074/jbc.M113.523209.Epub2013Nov19
  • Peer Reviewed
• [Journal Article] Structural insight into maintenance methy lation by mouse DNA methyltransfe rase 1 (Dnmt1) (2011)
  • Author(s): Takeshita K, Suetake I, Yamashita E, Suga M, Narita H, Nakagawa A, Tajima S
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108(22)(Epub 2011 Apr 25) Pages: 9055-9
  • DOI: 10.1073/pnas.1019629108
  • Peer Reviewed
• [Presentation] Dnmt1によるDNA維持メチル化活性は領域の大きな再配置を伴う反応である (2012)
  • Author(s): 末武勲、中村達郎、ベルキュレクアハメトジャン、竹下浩平、中川敦史、田嶋正三
  • Organizer: 第6回日本エヒジェネティクス研究会年会
  • Place of Presentation: 学術総合センター
  • Year and Date: 20120514-15
• [Presentation] Dnmt1のX線結晶構造から考察する維持メチル化機構 (2011)
  • Author(s): 竹下浩平
  • Organizer: 神経科学と構造生物学の融合J(大阪大学蛋白質研究所セミナー・包括脳ネットワーク研究会)
  • Place of Presentation: (岡崎コンファレンスセンター)
  • Year and Date: 20111121-22
• [Presentation] X線結晶構造から見るDnmt1のエピジエネティックマーク継承のメカニズム (2011)
  • Author(s): 竹下浩平、末武勲、山下栄樹、菅倫寛、成田宏隆、中川敦史、田嶋正三
  • Organizer: 第49回生物物理学会年会
  • Place of Presentation: 兵庫県立大学書写キャンパス
  • Year and Date: 20110916-18
• [Presentation] Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (2011)
  • Author(s): Takeshita K, Suetake, I., Yamashita, E., Suga, Narita, H., Nakagawa, A., Tajima S.
  • Organizer: International Union of Crystallography (IUCr)
  • Place of Presentation: Madrid Spain
  • Year and Date: 20110822-30
• [Presentation] Dnmt1によるメチル化模様維持機構に関する構造生物学的研究 (2011)
  • Author(s): 竹下浩平、末武勲、山下栄樹、菅倫寛、成田宏隆、中川敦史、田嶋正三
  • Organizer: 第11回日本蛋白質科学会年会
  • Place of Presentation: ホテル阪急エキスポミーク
  • Year and Date: 20110607-09
• [Presentation] X線結晶構造から考察するDnmt1による維持メチル化機構 (2011)
  • Author(s): 竹下浩平、末武勲、山下栄樹、菅倫寛、成田宏隆、中川敦史、田嶋正三
  • Organizer: 第5回日本エヒジェネティクス研究会年会
  • Place of Presentation: KKR熊本
  • Year and Date: 20110519-20
• [Remarks] 大阪大学蛋白質研究所・最新研究成果(2011) Structural insight into maintenance methylation by mouse Dnmt1
  • URL: http://www.protein.osaka-u.ac.jp/jpn/achievement/papers/the-dna-methyltransferase-dnmt.php
• [Remarks] 大型放射光施設SPring-8プレスリリース・トピックス(2011)ゲノムのメチル化模様維持を触媒する酵素の立体構造を解明-がん細胞を制御する創薬の開発につながる-(プレスリリース)
  • URL: http://www.spring8.or.jp/ja/news_publications/press_release/2011/110426/