X-ray crystallographic study of Bloom syndrome helicase BLM and its role in prevention of tumorigenesis.

• Project/Area Number: 25440024
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Kitano Ken 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (40346309)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: Ｘ線構造解析 / ブルーム症候群 / ヘリカーゼ / ホリデイジャンクション / タンパク質 / DNA / ラディキシン / マトリックスメタロプロテアーゼ / ホスホジエステラーゼ / 結晶化 / X線構造解析

Outline of Final Research Achievements

Bloom syndrome is a rare cancer-predisposition disorder caused by mutations of the Bloom syndrome protein (BLM). In this study, structural and biochemical studies of human BLM helicase were performed. New information about the reaction mechanism of BLM helicase toward Holliday junction (a repair intermediate in the DNA double-stranded break repair) was obtained.

Research Products

• [Journal Article] MT1-MMP recognition by ERM proteins and its implication in CD44 shedding. (2015)
  • Author(s): Shin-ichi Terawaki, Ken Kitano, Miki Aoyama, Tomoyuki Mori, Toshio Hakoshima
  • Journal Title: Genes to Cells Volume: 20(10) Issue: 10 Pages: 847-859
  • DOI: 10.1111/gtc.12276
  • Peer Reviewed / Open Access
• [Journal Article] Structural mechanisms of human RecQ helicases WRN and BLM. (2014)
  • Author(s): Ken Kitano
  • Journal Title: Frontiers in Genetics Volume: 5 Pages: 366-366
  • DOI: 10.3389/fgene.2014.00366
  • NAID: 120005841619
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Crystallographic Studies of Human RecQ Helicases WRN and BLM (2014)
  • Author(s): 北野健
  • Journal Title: Nihon Kessho Gakkaishi Volume: 56 Issue: 2 Pages: 133-138
  • DOI: 10.5940/jcrsj.56.133
  • NAID: 130004552886
  • ISSN: 0369-4585, 1884-5576
  • Peer Reviewed / Open Access
• [Journal Article] Structural Basis for the Specific Inhibition of Heterotrimeric G Protein by a Cyclic Peptide (2014)
  • Author(s): 北野 健
  • Journal Title: Seibutsu Butsuri Volume: 54 Issue: 5 Pages: 265-266
  • DOI: 10.2142/biophys.54.265
  • NAID: 130004693954
  • ISSN: 0582-4052, 1347-4219
  • Peer Reviewed / Open Access
• [Journal Article] Structure of the RecQ C-terminal domain of human Bloom syndrome protein. (2013)
  • Author(s): Kim SY, Hakoshima T, Kitano K.
  • Journal Title: Sci Rep. Volume: 3 Issue: 1 Pages: 3294-3294
  • DOI: 10.1038/srep03294
  • NAID: 120005841622
  • Peer Reviewed
• [Presentation] ヒト RecQ ヘリカーゼ WRN と BLM の結晶構造解析. (2016)
  • Author(s): 北野 健, 箱嶋敏雄
  • Organizer: 平成 28 年度 日本結晶学会年会
  • Place of Presentation: 茨城県立県民文化センター (茨城県水戸市)
  • Year and Date: 2016-11-17
• [Presentation] Werner syndrome helicase possesses a compact "DNA zip-slider" domain. (2016)
  • Author(s): Ken Kitano
  • Organizer: 45th Annual Meeting of the American Aging Association
  • Place of Presentation: Bell Harbor International Conference Center (Seattle, USA)
  • Year and Date: 2016-06-01
  • Int'l Joint Research
• [Presentation] Structural mechanisms of human RecQ helicases WRN and BLM. (2016)
  • Author(s): Ken Kitano
  • Organizer: 3rd International Meeting on RECQ Helicases in Biology and Medicine (RECQ2016)
  • Place of Presentation: Fred Hutchinson Cancer Research Center (Seattle, USA)
  • Year and Date: 2016-05-28
  • Int'l Joint Research / Invited
• [Presentation] Discovery of a 'DNA zip-slider' domain in human RecQ helicases WRN and BLM. (2015)
  • Author(s): Ken Kitano, Sun-Yong Kim, Toshio Hakoshima
  • Organizer: The International Chemical Congress of Pacific Basin Societies 2015
  • Place of Presentation: Hawaii Convention Center (Honolulu, USA)
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Structural study of human RecQ helicases WRN and BLM. (2014)
  • Author(s): Ken Kitano, Sun-Yong Kim, Toshio Hakoshima
  • Organizer: 第87回 日本生化学会大会
  • Place of Presentation: 国立京都国際会館 (京都府京都市)
  • Year and Date: 2014-10-15 – 2014-10-18
  • Invited
• [Presentation] Structural basis for the membrane-targeting of Rac-specific guanine nucleotide exchange factors, Tiam1/2. (2014)
  • Author(s): Shin‐ichi Terawaki, Ken Kitano, Tomoyuki Mori, Yoshiki Higuchi, Norimichi Itoh, Takashi Watanabe, Kozo Kaibuchi, Toshio Hakoshima
  • Organizer: 6th International Society for Neurochemistry (ISN) Special Conference
  • Place of Presentation: 東京大学 (東京都文京区)
  • Year and Date: 2014-09-20 – 2014-09-22
• [Presentation] Structural study of Bloom syndrome protein. (2014)
  • Author(s): Sun-Yong Kim, Toshio Hakoshima, Ken Kitano
  • Organizer: Biophysical Society 58th Annual Meeting
  • Place of Presentation: San Francisco, CA, USA.
• [Presentation] Radixin と MT1-MMP との複合体のＸ線結晶構造解析 (2013)
  • Author(s): 寺脇慎一, 北野 健, 森 智行, 青山美樹, 箱嶋敏雄
  • Organizer: 平成25年度 日本結晶学会年会
  • Place of Presentation: 熊本大学, 熊本市
• [Presentation] Protein interaction between NADH oxidase and AhpC (Prx) from Amphibacillus xylanus. (2013)
  • Author(s): Daichi Mochizuki, Toshiaki Arai, Keita Hara, Takashi Matsumoto, Ken Kitano, Tamotsu Zako, Masafumi Odaka, Masafumi Yohda, Junichi Sato, Shinji Kawasaki, Shuji Kanamaru, Fumio Arisaka, Youichi Niimura
  • Organizer: 21st International Conference on Analytical Ultracentrifugation, Hydrodynamics, Thermodynamics and Complementary Methods（AUC2013）
  • Place of Presentation: ホテルニューアカオ, 静岡県熱海市
• [Presentation] 膜貫通型プロテアーゼ MT1-MMP の ERM 蛋白質による細胞骨格連結の構造的基盤 (2013)
  • Author(s): 寺脇慎一, 北野 健, 青山美樹, 箱嶋敏雄
  • Organizer: 第13回 日本蛋白質科学会年会
  • Place of Presentation: とりぎん文化会館, 鳥取市
• [Presentation] Allosteric inhibition of heterotrimeric Gq protein by a small molecule. (2013)
  • Author(s): Ken Kitano, Akiyuki Nishimura, Toshio Hakoshima, Hiroshi Itoh.
  • Organizer: EMBO Conference on Allosteric Interactions in Cell Signaling and Regulation
  • Place of Presentation: Institut Pasteur, Paris, France
• [Remarks] マウス由来ラディキシン FERM ドメインと MT1-MMP 細胞質ペプチドの複合体結晶構造
  • URL: http://www.rcsb.org/pdb/explore.do?structureId=3X23
• [Remarks] ヒト由来ホスホジエステラーゼ-12 (PDE12) の結晶構造
  • URL: http://www.rcsb.org/pdb/explore.do?structureId=4ZKF
• [Remarks] ヒ酸結合型 BLM RQC ドメインの結晶構造
  • URL: http://www.rcsb.org/pdb/explore.do?structureId=3WE3