Molecular Mechanisms of RAD52-Mediated Homologous Recombination

• Project/Area Number: 21770127
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Structural biochemistry
• Research Institution: Waseda University
• Principal Investigator: KAGAWA Wataru Waseda University, 理工学術院, 助教 (70415123)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 相同組換え / X線結晶構造解析 / 一本鎖DNA / タンパク質と酵素 / 核酸 / 構造生物学 / X線結晶解析 / 遺伝子及び染色体 / 分子認識

Research Abstract

Homologous recombination is an important mechanism for genomic stability. To understand the underlying molecular mechanisms, three-dimensional structures of RAD52-single-stranded DNA complexes were solved by X-ray crystallography. The single-stranded DNA bound to RAD52 has a characteristic, right-handed helical structure, with bases exposed to the solvent. This structure appears suitable for the efficient search of homologous DNA sequences. The present structure provides the first clear view of how DNA homology search takes place.

Research Products

• [Journal Article] Structural and biochemical analyses of the human PAD4 variant encoded by a functional haplotype gene. (2011)
  • Author(s): Horikoshi N, Tachiwana H, Saito K, Osakabe A, Sato M, Yamada M, Akashi S, Nishimura Y, Kagawa W, Kurumizaka H
  • Journal Title: Acta Crystallogr D Biol Crystallogr 67 Pages: 112-118
  • Peer Reviewed
• [Journal Article] Structural and biochemical analyses of the human PAD4 variant encoded by a functional haplotype gene. (2011)
  • Author(s): Horikoshi N, Tachiwana H, Saito K, et al.
  • Journal Title: Acta Crystallogr D Biol Crystallogr Volume: 67 Pages: 112-118
  • Peer Reviewed
• [Journal Article] 発癌防御に重要な相同組換えの分子機構 (2010)
  • Author(s): 齋藤健吾、香川亘、胡桃坂仁志
  • Journal Title: 最新医学 65巻 Pages: 76-88
  • Peer Reviewed
• [Journal Article] Structural basis of instability of the nucleosome containing a testis-specific histone variant, human H3T. (2010)
  • Author(s): Tachiwana H, Kagawa W, Osakabe A, Kawaguchi K, Shiga T, Hayashi-Takanaka Y, Kimura H, Kurumizaka H
  • Journal Title: Proc Natl Acad Sci USA 107 Pages: 10454-10459
  • Peer Reviewed
• [Journal Article] The putative nuclear localization signal of the human RAD52 protein is a potential sumoylation site. (2010)
  • Author(s): Saito K, Kagawa W, Suzuki T, Suzuki H, Yokoyama S, Saitoh H, Tashiro S, Dohmae N, Kurumizaka H
  • Journal Title: J Biochem 147 Pages: 833-842
  • NAID: 10027876425
  • Peer Reviewed
• [Journal Article] Enhancing survival of mouse oocytes following chemotherapy or aging by targeting Bax and Rad51. (2010)
  • Author(s): Kujjo LL, Laine T, Pereira RJ, Kagawa W, Kurumizaka H, Yokoyama S, Perez GI
  • Journal Title: PLoS One 5
  • Peer Reviewed
• [Journal Article] Dynamics in the transmission of genetic information : from meiosis to postmeiotic events. (2010)
  • Author(s): Kagawa W, Kurumizaka H
  • Journal Title: FEBS J 277 Pages: 564-564
  • Peer Reviewed
• [Journal Article] From meiosis to postmeiotic events : Uncovering the molecular roles of the meiosis-specific recombinase Dmc1. (2010)
  • Author(s): Kagawa W, Kurumizaka H
  • Journal Title: FEBS J 277 Pages: 590-598
  • Peer Reviewed
• [Journal Article] 発癌防御に重要な相同組換えの分子機構 (2010)
  • Author(s): 齋藤健吾、香川亘、胡桃坂仁志
  • Journal Title: 最新医学 Volume: 65 Pages: 76-88
  • Peer Reviewed
• [Journal Article] Structural basis of instability of the nucleosome containing a testis-specific histone variant, human H3T (2010)
  • Author(s): Tachiwana H, Kagawa W, Osakabe A, et al.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 107 Pages: 10454-10459
  • Peer Reviewed
• [Journal Article] The putative nuclear localization signal of the human RAD52 protein is a potential sumoylation site (2010)
  • Author(s): Saito K, Kagawa W, Suzuki T, et al.
  • Journal Title: J Biochem Volume: 147 Pages: 833-842
  • NAID: 10027876425
  • Peer Reviewed
• [Journal Article] 発癌防御に重要な相同組換えの分子機構 (2010)
  • Author(s): 齋藤健吾、香川亘、胡桃坂仁志
  • Journal Title: 最新医学 65(発行予定)
  • Peer Reviewed
• [Journal Article] The putative nuclear Iocalization signal of the human RAD52 protein is a potential sumoylation site (2010)
  • Author(s): Saito K, Kagawa W, et al.
  • Journal Title: Journal of Biochemistry (発行予定)
  • Peer Reviewed
• [Journal Article] Enhancing survival of mouse oocytes following chemotherapy or aging by targeting Bax and Rad51 (2010)
  • Author(s): Kujjo LL, Laine T, Pereira RJ, Kagawa W, et al.
  • Journal Title: PLoS One 5
  • Peer Reviewed
• [Journal Article] Dynamics in the transmission of genetic information : from meiosis to postmeiotic events (2010)
  • Author(s): Kagawa W, Kurumizaka H
  • Journal Title: FEBS Journal 277 Pages: 564-564
  • Peer Reviewed
• [Journal Article] From meiosis to postmeiotic events : uncovering the molecular roles of the meiosis-specific recombinase Dmc1 (2010)
  • Author(s): Kagawa W, Kurumizaka H
  • Journal Title: FEBS Journal 277 Pages: 590-598
  • Peer Reviewed
• [Presentation] Roles of the N-terminal and C-terminal domains of the Rad52 protein in homologous recombinational repair (2011)
  • Author(s): Kagawa W, Saito K, Sugiyama S, Onodera K, Kurumizaka H
  • Organizer: International Symposium on the Physicochemical Field for Genet is Activities
  • Place of Presentation: Awaji Yumebutai
  • Year and Date: 2011-01-23
• [Presentation] The Crystal Structure of Centromere Specific Nucleosome (2011)
  • Author(s): Tachiwana H, Kagawa W, Shiga, T, et al.
  • Organizer: International Symposium on the Physicochemical Field for Genetic Activities
  • Place of Presentation: Awaji Yumebutai
  • Year and Date: 2011-01-23
• [Presentation] C-terminal Tail of Histone H2AX Reduces Intra-nucleosome Array Interaction (2011)
  • Author(s): Suka N
  • Organizer: International Symposium on the Physicochemical Field for Genetic Activities
  • Place of Presentation: Awaji Yumebutai
  • Year and Date: 2011-01-23
• [Presentation] Roles of the N-terminal and C-terminal domains of the Rad52 protein in homologous recombinational repair. (2011)
  • Author(s): Kagawa W, Saito K, Sugiyama S, Onodera K, Kurumizaka H
  • Organizer: International Symposium on the Physicochemical Field for Genetic Activities
  • Place of Presentation: Awaji Island
• [Presentation] CENP-Aターゲッティングドメインを含むH3変異体が形成するヌクレオソームのX線結晶構造解析 (2010)
  • Author(s): 志賀達也、立和名博昭、香川亘、越阪部晃永、胡桃坂仁志
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-07
• [Presentation] セントロメア領域に特異的なヌクレオソームのX線結晶構造解析 (2010)
  • Author(s): 立和名博昭、香川亘、志賀達也, 他
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-07
• [Presentation] ファンコニ貧血原因遺伝子産物FANCD2およびFANCIの複合体形成と機能解析 (2010)
  • Author(s): 佐藤浩一、戸田和江、古越聡, 他
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-07
• [Presentation] ヒストンバリアントを含むヌクレオソームの構造多様性と機能 (2010)
  • Author(s): 胡桃坂仁志、立和名博昭、香川亘, 他
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-07
• [Presentation] 酵母とヒトDNA修復タンパク質Rad52の機能ドメイン解析 (2010)
  • Author(s): 香川亘、齋藤健吾、杉山修世、小野寺圭一、胡桃坂仁志
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-07
• [Presentation] DNA修復タンパク質RAD52の翻訳後修飾による機能制御機構の解析 (2010)
  • Author(s): 齋藤健吾、香川亘、鈴木健裕, 他
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-07
• [Presentation] 出芽酵母Rad52の第二DNA結合部位も相同組換えに必要である (2010)
  • Author(s): 新井直人、香川亘、新宮良宣、美川務、胡桃坂仁志、柴田武彦
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-07
• [Presentation] ヒトと酵母のDNA修復タンパク質Rad52の機能比較 (2010)
  • Author(s): 齋藤健吾、香川亘、杉山修世、小野寺圭一、胡桃坂仁志
  • Organizer: 第9回核ダイナミクス研究会
  • Place of Presentation: ラフォーレ修善寺
  • Year and Date: 2010-05-27
• [Presentation] ブーケ配向形成因子S.japonicus Bqt1-Bqt2複合体の生化学的解析 (2010)
  • Author(s): 市川雄一、香川亘、近重裕次、平野泰弘、原口徳子、平岡泰、胡桃坂仁志
  • Organizer: 第9回核ダイナミクス研究会
  • Place of Presentation: ラフォーレ修善寺
  • Year and Date: 2010-05-27
• [Presentation] シトルリン化タンパク質PAD4のSNP変異体の解析 (2010)
  • Author(s): 堀越直樹、立和名博昭、斎藤健吾、香川亘, 他
  • Organizer: 第9回核ダイナミクス研究会
  • Place of Presentation: ラフォーレ修善寺
  • Year and Date: 2010-05-27
• [Presentation] Rad52タンパク質のDNA positive supercoiling活性の役割 (2010)
  • Author(s): 香川亘、齊藤健吾、胡桃坂仁志
  • Organizer: 第9回核ダイナミクス研究会
  • Place of Presentation: ラフォーレ修善寺
  • Year and Date: 2010-05-27
• [Presentation] ヒストンバリアントH3Tを含むヌクレオソームの構造解析および生化学的解析 (2010)
  • Author(s): 立和名博昭、香川亘、越阪部晃永, 他
  • Organizer: 第9回核ダイナミクス研究会
  • Place of Presentation: ラフォーレ修善寺
  • Year and Date: 2010-05-27
• [Presentation] Structural and biochemical studies of the human Rad52 protein and its implications for homologous recombination (2010)
  • Author(s): 香川亘、齋藤健吾、胡桃坂仁志
  • Organizer: The 6th NIRS International Open Laboratory Workshop
  • Place of Presentation: 放射線医学総合研究所
  • Year and Date: 2010-03-24
• [Presentation] 相同DNA組換えにおける2種の相同DNA対合蛋白質の役割分担 (2010)
  • Author(s): 柴田武彦、新井直人、新宮良宜、増田ときは、香川亘, 他
  • Organizer: 第27回染色体ワークショップ
  • Place of Presentation: 御殿場高原ホテル
  • Year and Date: 2010-01-22
• [Presentation] ブーケ配向形成因子S. japonicus Bqt1-Bqt2複合体の精製および機能解析 (2010)
  • Author(s): 市川雄一、香川亘、近重裕次、平野泰弘、原口徳子、平岡泰、胡桃坂仁志
  • Organizer: 第27回染色体ワークショップ
  • Place of Presentation: 御殿場高原ホテル
  • Year and Date: 2010-01-21
• [Presentation] セントロメア特異的なCENP-Aヌクレオソームの生化学的解析 (2010)
  • Author(s): 立和名博昭、川口紘一郎、越阪部晃永、志賀達也、香川亘、胡桃坂仁志
  • Organizer: 第27回染色体ワークショップ
  • Place of Presentation: 御殿場高原ホテル
  • Year and Date: 2010-01-20
• [Presentation] 酵母とヒトDNA修復タンパク質Rad52の機能ドメイン解析 (2010)
  • Author(s): 香川亘、齋藤健吾、杉山修世、小野寺圭一、胡桃坂仁志
  • Organizer: BMB2010
  • Place of Presentation: 神戸
• [Presentation] Rad52タンパク質のDNA positive supercoiling活性の役割 (2010)
  • Author(s): 香川亘、齋藤健吾、杉山修世、胡桃坂仁志
  • Organizer: 第9回核ダイナミクス研究会
  • Place of Presentation: 修善寺
• [Presentation] Structural and biochemical studies of the human Rad52 protein and its implications for homologous recombination. (2010)
  • Author(s): Kagawa W
  • Organizer: The 6th NIRS International Open Laboratory Workshop
  • Place of Presentation: 稲毛(千葉)
• [Presentation] 大腸菌染色体分配に関わる候補因子MigP(YncE)の構造生物学的解析 (2009)
  • Author(s): 香川亘、佐川智彦、仁木宏典、胡桃坂仁志
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-12
• [Presentation] DNA修復タンパク質Rad52のヒトと酵母における機能比較 (2009)
  • Author(s): 齋藤健吾、香川亘、胡桃坂仁志
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-12
• [Presentation] 出芽酵母Rad52-Rad51複合体によるD-loop形成においてRad52は二本鎖DNAの結合に働く (2009)
  • Author(s): 新井直人、番川亘、美川務、胡桃坂仁志、柴田武彦
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-11
• [Presentation] DNA配列を改変したヌクレオソーム複合体の生産技術開発 (2009)
  • Author(s): 若森昌聡、須賀則之、藤川乃り映、香川亘, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-11
• [Presentation] セントロメア特異的H3バリアントCENP-Aを含むヌクレオソームの構造解析 (2009)
  • Author(s): 立和名博昭、番川亘、志賀達也、川口紘一郎、越阪部晃永、胡桃坂仁志
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-10
• [Presentation] クロマチンの基盤構造であるヌクレオソームの機能・構造解析 (2009)
  • Author(s): 胡桃坂仁志、立和名博昭、越阪部晃永、川口紘一郎、香川亘
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-10
• [Presentation] ブーケ配向形成因子S. japonicus Bqt1-Bqt2複合体の大量精製および生化学的解析 (2009)
  • Author(s): 市川雄一、香川亘、近重裕次、原口徳子、平岡泰、胡桃坂仁志
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-09
• [Presentation] ヒトと酵母のDNA修復タンパク質Rad52の機能比較 (2009)
  • Author(s): 香川亘、齋藤健吾、胡桃坂仁志
  • Organizer: 第20回DNA複製・組換え・修復ワークショップ
  • Place of Presentation: 琵琶湖カンファレンスセンター
  • Year and Date: 2009-11-03
• [Presentation] ヒストンバリアントH3tを含むヌクレオソームの立体構造とその機能解析 (2009)
  • Author(s): 立和名博昭、志賀達也、川口紘一郎、越阪部晃永、木村宏、香川亘, 他
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2009-10-23
• [Presentation] 相同DNA組換えにおける天然変性領域の機能 (2009)
  • Author(s): 柴田武彦、新井直人、凌楓、香川亘、胡桃坂仁志、井上仁、新宮良宣、美川務
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2009-10-21
• [Presentation] RAD52の立体構造に基づく相同組換え反応機構の解析 (2009)
  • Author(s): 香川亘、齋藤健吾、胡桃坂仁志
  • Organizer: 第8回核ダイナミクス研究会
  • Place of Presentation: ラフォーレ修著寺
  • Year and Date: 2009-06-18
• [Presentation] ヒトSUMO化RAD52の生化学的および物理化学的解析 (2009)
  • Author(s): 齋藤健吾、香川亘、胡桃坂仁志
  • Organizer: 第8回核ダイナミクス研究会
  • Place of Presentation: ラフォーレ修善寺
  • Year and Date: 2009-06-18
• [Presentation] 大腸菌染色体分配に関わる候補因子MigP(YncE)の構造生物学的解析 (2009)
  • Author(s): 香川亘、佐川智彦、仁木宏典、胡桃坂仁志
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] ヒトと酵母のDNA修復タンパク質Rad52の機能比較 (2009)
  • Author(s): 香川亘、齋藤健吾、杉山修世、胡桃坂仁志
  • Organizer: 第20回DNA複製・組換え・修復ワークショップ
  • Place of Presentation: 琵琶湖コンファレンスセンター
• [Presentation] RAD52の立体構造に基づく相同組換え反応機構の解析 (2009)
  • Author(s): 香川亘、齋藤健吾、胡桃坂仁志
  • Organizer: 第8回核ダイナミクス研究会
  • Place of Presentation: 修善寺
• [Remarks]
  • URL: http://www.eb.waseda.ac.jp/kurumizaka/