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Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.
Ishiyama, Satoshi; Nishiyama, Atsuya; Saeki, Yasushi; Moritsugu, Kei; Morimoto, Daichi; Yamaguchi, Luna; Arai, Naoko; Matsumura, Rumie; Kawakami, Toru; Mishima, Yuichi; Hojo, Hironobu; Shimamura, Shintaro; Ishikawa, Fuyuki; Tajima, Shoji; Tanaka, Keiji; Ariyoshi, Mariko; Shirakawa, Masahiro; Ikeguchi, Mitsunori; Kidera, Akinori; Suetake, Isao; Arita, Kyohei; Nakanishi, Makoto.
Afiliação
  • Ishiyama S; Structure Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
  • Nishiyama A; Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
  • Saeki Y; Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
  • Moritsugu K; Computational Life Science Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
  • Morimoto D; Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto-Daigaku Katsura, Nishikyo-Ku, Kyoto 615-8510, Japan.
  • Yamaguchi L; Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
  • Arai N; Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
  • Matsumura R; Structure Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
  • Kawakami T; Laboratory of Protein Organic Chemistry, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
  • Mishima Y; Laboratory of Epigenetics, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
  • Hojo H; Laboratory of Protein Organic Chemistry, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
  • Shimamura S; Second Department of Internal Medicine, Nagasaki University, Nagasaki 852-8501, Japan.
  • Ishikawa F; Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
  • Tajima S; Laboratory of Epigenetics, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
  • Tanaka K; Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
  • Ariyoshi M; Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto-Daigaku Katsura, Nishikyo-Ku, Kyoto 615-8510, Japan.
  • Shirakawa M; Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto-Daigaku Katsura, Nishikyo-Ku, Kyoto 615-8510, Japan.
  • Ikeguchi M; Computational Life Science Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
  • Kidera A; Computational Life Science Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
  • Suetake I; Laboratory of Epigenetics, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan; CREST, JST, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan. Electronic address: suetake@protein.osaka-u.ac.jp.
  • Arita K; Structure Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; PRESTO, JST, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan. Electronic address: aritak@tsurumi.yokohama-cu.ac.jp.
  • Nakanishi M; Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electr
Mol Cell ; 68(2): 350-360.e7, 2017 Oct 19.
Article em En | MEDLINE | ID: mdl-29053958
ABSTRACT
The proper location and timing of Dnmt1 activation are essential for DNA methylation maintenance. We demonstrate here that Dnmt1 utilizes two-mono-ubiquitylated histone H3 as a unique ubiquitin mark for its recruitment to and activation at DNA methylation sites. The crystal structure of the replication foci targeting sequence (RFTS) of Dnmt1 in complex with H3-K18Ub/23Ub reveals striking differences to the known ubiquitin-recognition structures. The two ubiquitins are simultaneously bound to the RFTS with a combination of canonical hydrophobic and atypical hydrophilic interactions. The C-lobe of RFTS, together with the K23Ub surface, also recognizes the N-terminal tail of H3. 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. Our results therefore shed light on the essential role of a unique ubiquitin-binding module in DNA methylation maintenance.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Histonas / Metilação de DNA / Ubiquitina / DNA (Citosina-5-)-Metiltransferases Limite: Animals / Humans Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Histonas / Metilação de DNA / Ubiquitina / DNA (Citosina-5-)-Metiltransferases Limite: Animals / Humans Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Japão