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Hunting and analysis of novel genes causing Fanconi anemia

Research Project

Project/Area Number 15H01738
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionKyoto University

Principal Investigator

Takata Minoru  京都大学, 放射線生物研究センター, 教授 (30281728)

Co-Investigator(Kenkyū-buntansha) 石合 正道  京都大学, 放射線生物研究センター, 准教授 (90298844)
佐藤 浩一  早稲田大学, 理工学術院, 次席研究員(研究院助教) (60708585)
Co-Investigator(Renkei-kenkyūsha) Hosokawa Hiroshi  京都大学, 情報学研究科, 講師 (90359779)
Maegawa Shingo  京都大学, 情報学研究科, 助教 (30467401)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥46,020,000 (Direct Cost: ¥35,400,000、Indirect Cost: ¥10,620,000)
Fiscal Year 2017: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Fiscal Year 2016: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
Fiscal Year 2015: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Keywordsファンコニ貧血 / FA経路 / RFWD3 / ユビキチン化 / 原因遺伝子 / DNA損傷修復 / 相同組換え / ゼブラフィッシュ / ゲノムシーケンス / DNA修復 / モノユビキチン化 / 次世代シーケンサー / アレイCGH / 先天性骨髄不全
Outline of Final Research Achievements

We analyzed unclassified FA cases and found that many of them are caused by slicing defects in known FA genes that were not evident in whole exome sequencing. We also identified two siblings that carry biallelic mutations in an important DNA repair factor. In 20 Indian FA cases, we identified frequent specific FANCL mutations, which are very rare in other ethnic groups. We generated novel zebrafish FANCT or FANCD2 model that resulted in 100% male fish. In collaborative efforts with German group, we established mutations in RFWD3 gene encoding a E3 ubiquitin ligase causes FA phenotype and that its targets are critical homologous recombination regulators, RPA and RAD51.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (47 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (7 results) Journal Article (17 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 17 results,  Open Access: 12 results,  Acknowledgement Compliant: 4 results) Presentation (16 results) (of which Int'l Joint Research: 10 results,  Invited: 9 results) Book (2 results) Remarks (5 results)

  • [Int'l Joint Research] University of Wuruzburg(Germany)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] National Institute of Immunohaematology(India)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] National Institute of Health(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] National Institute of Immunohaematology(India)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of Wurzburg(Germany)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] National Institute of Aging(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Nantional Institute of Immunohaematology(India)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Replication stress induces accumulation of FANCD2 at central region of large fragile genes.2018

    • Author(s)
      Okamoto Y, Iwasaki WM, Kugou K, Takahashi KK, Oda A, Sato K, Kobayashi W, Kawai H, Sakasai R, Takaori-Kondo A, Yamamoto T, Kanemaki MT, Taoka M, Isobe T, Kurumizaka H, Innan H, Ohta K, Ishiai M, Takata M.
    • Journal Title

      Nucleic Acids Res.

      Volume: 46(6) Issue: 6 Pages: 2932-2944

    • DOI

      10.1093/nar/gky058

    • NAID

      120006488604

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PARI regulates stalled replication fork proessing to maintain genome stability upon replication stress in mice2017

    • Author(s)
      Ayako L. Mochizuki, Ami Katanaya, Eri Hayashi, Mihoko Hosokawa, Emiko Moribe, Akira Motegi, Masamichi Ishiai,Minoru Takata, Gen Kondoh, Hitomi Watanabe, Norio Nakatsuji, and Shinichiro Chuma
    • Journal Title

      Mol. Cell. Biol

      Volume: 37 (23) Issue: 23

    • DOI

      10.1128/mcb.00117-17

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia.2017

    • Author(s)
      Kerstin Knies, Shojiro Inano, Maria Ramirez, Masamichi Ishiai, Jordi Suralles, Minoru Takata, and Detlev Schindler.
    • Journal Title

      Journal of Clinical Investigation

      Volume: 127 Issue: 8 Pages: 3013-3027

    • DOI

      10.1172/jci92069

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] RFWD3-Mediated Ubiquitination Promotes Timely Removal of Both RPA and RAD51 from DNA Damage Sites to Facilitate Homologous Recombination2017

    • Author(s)
      Inano Shojiro、Sato Koichi、Katsuki Yoko、Kobayashi Wataru、Tanaka Hiroki、Nakajima Kazuhiro、Nakada Shinichiro、Miyoshi Hiroyuki、Knies Kerstin、Takaori-Kondo Akifumi、Schindler Detlev、Ishiai Masamichi、Kurumizaka Hitoshi、Takata Minoru
    • Journal Title

      Molecular Cell

      Volume: 66 Issue: 5 Pages: 622-634

    • DOI

      10.1016/j.molcel.2017.04.022

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Common Variable Immunodeficiency Caused by FANC Mutations2017

    • Author(s)
      Sekinaka Y., Mitsuiki N., Imai K., Yabe M., Yabe H., Mitsui-Sekinaka K., Honma K., Takagi M., Arai A., Yoshida K., Okuno Y., Shiraishi Y., Chiba K., Tanaka H., Miyano S., Muramatsu H., Kojima S., Hira A., Takata M., Ohara O., Ogawa S., Morio T., Nonoyama S.
    • Journal Title

      Journal of clinical immunology

      Volume: 37 Issue: 5 Pages: 434-444

    • DOI

      10.1007/s10875-017-0396-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes.2017

    • Author(s)
      Muramatsu H, Okuno Y, Yoshida K, Shiraishi Y, Doisaki S, Narita A, Sakaguchi H, Kawashima N, Wang X, Xu Y, Chiba K, Tanaka H, Hama A, Sanada M, Takahashi Y, Kanno H, Yamaguchi H, Ohga S, Manabe A, Harigae H, Kunishima S, Ishii E, Kobayashi M, Koike K, Watanabe K, Ito E, Takata M, Yabe M, Ogawa S, Miyano S, Kojima S.
    • Journal Title

      Genet Med.

      Volume: - Issue: 7 Pages: 796-802

    • DOI

      10.1038/gim.2016.197

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Bloom syndrome complex promotes FANCM recruitment to stalled replication forks and facilitates both repair and traverse of DNA interstrand crosslinks.2016

    • Author(s)
      Chen Ling, Jing Huang, Zhijiang Yan, Yongjiang Li, Mioko Ohzeki, Masamichi Ishiai, Dongyi Xu, Minoru Takata, Michael Seidman, and Weidong Wang.
    • Journal Title

      Cell Discov

      Volume: 2 Issue: 1 Pages: 16047-16047

    • DOI

      10.1038/celldisc.2016.47

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Homologous Recombination and Translesion DNA Synthesis Play Critical Roles on Tolerating DNA Damage Caused by Trace Levels of Hexavalent Chromium.2016

    • Author(s)
      Tian X, Patel K, Ridpath JR, Chen Y, Zhou YH, Neo D, Clement J, Takata M, Takeda S, Sale J, Wright FA, Swenberg JA, Nakamura J
    • Journal Title

      PLoS One

      Volume: 11 Issue: 12 Pages: e0167503-e0167503

    • DOI

      10.1371/journal.pone.0167503

    • NAID

      120005980904

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end.2016

    • Author(s)
      Sato K, Shimomuki M, Katsuki Y, Takahashi D, Kobayashi W, Ishiai M, Miyoshi H, Takata M, Kurumizaka H.
    • Journal Title

      Nucleic Acids Res

      Volume: 44 Issue: 22 Pages: 10758-10771

    • DOI

      10.1093/nar/gkw876

    • NAID

      120006318854

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Defects in HR repair behind the human diseases: FA and HBOC. Endocrine Related Cancer.2016

    • Author(s)
      Katsuki Y, Takata M.
    • Journal Title

      Endocrine Related Cancer.

      Volume: 23 Issue: 10 Pages: T19-T37

    • DOI

      10.1530/erc-16-0221

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Poor recognition of O6-isopropyl dG by MGMT triggers double strand break-mediated cell death and micronucleus induction in FANC-deficient cells.2016

    • Author(s)
      Hashimoto K, Sharma V, Sasanuma H, Tian X, Takata M, Takeda S, Swenberg JA, Nakamura J
    • Journal Title

      Oncotarget

      Volume: 7 Issue: 37 Pages: 59795-59808

    • DOI

      10.18632/oncotarget.10928

    • NAID

      120005980805

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The phenotype and clinical course of Japanese Fanconi Anaemia infants is influenced by patient, but not maternal ALDH2 genotype.2016

    • Author(s)
      Yabe M, Yabe H, Morimoto T, Fukumura A, Ohtsubo K, Koike T, Yoshida K, Ogawa S, Ito E, Okuno Y, Muramatsu H, Kojima S, Matsuo K, Hira A, Takata M.
    • Journal Title

      Br J Haematol.

      Volume: 175 Issue: 3 Pages: 457-461

    • DOI

      10.1111/bjh.14243

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Human FAN1 promotes strand incision in 5'-flapped DNA complexed with RPA.2015

    • Author(s)
      Takahashi D, Sato K, Hirayama E, Takata M, Kurumizaka H.
    • Journal Title

      J Biochem

      Volume: 158 Issue: 3 Pages: 263-70

    • DOI

      10.1093/jb/mvv043

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pluripotent cell models of Fanconi anemia identify the early pathological defect in human hemoangiogenic progenitors.2015

    • Author(s)
      Suzuki NM, Niwa A, Yabe M, Hira A, Okada C, Amano N, Watanabe A, Watanabe K, Heike T, Takata M, Nakahata T, Saito MK
    • Journal Title

      Stem Cells Transl Med

      Volume: 4 Issue: 4 Pages: 333-338

    • DOI

      10.5966/sctm.2013-0172

    • NAID

      120005980869

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia.2015

    • Author(s)
      Hira A, Yoshida K, Sato K, Okuno Y, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Shimamoto A, Tahara H, Ito E, Kojima S, Kurumizaka H, Ogawa S, Takata M, Yabe H, Yabe M.
    • Journal Title

      Am J Hum Genet.

      Volume: 96(6) Issue: 6 Pages: 1001-7

    • DOI

      10.1016/j.ajhg.2015.04.022

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rad18 and Rnf8 facilitate homologous recombination by two distinct mechanisms, promoting Rad51 focus formation and suppressing the toxic effect of nonhomologous end-joining2015

    • Author(s)
      Michael Schmid, Akira Motegi (ほか総計106名、代表者は前から63番目)
    • Journal Title

      Cytogenet. Genome Res.

      Volume: 145 Issue: 2 Pages: 78-179

    • DOI

      10.1159/000430927

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Conserved overlapping gene arrangement, restricted expression and biochemical activities of DNA polymerase ν; (POLN).2015

    • Author(s)
      Takata KI, Tomida J, Reh S, Swanhart LM, Takata M, Hukriede NA, Wood RD.
    • Journal Title

      J Biol Chem

      Volume: 290 Issue: 40 Pages: 27278-93

    • DOI

      10.1074/jbc.m115.677419

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Pathogenesis of Fanconi anemia: an update.2017

    • Author(s)
      Minoru Takata
    • Organizer
      International Conference on “ Revolution of Laboratory Medicine In Modern Biology”
    • Place of Presentation
      Mumbai, India
    • Year and Date
      2017-02-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ICL修復因子SLX4はRNF168依存的なユビキチン化経路を介して損傷部位に集積する.2017

    • Author(s)
      勝木陽子, 安倍昌子, Haico van Attikum, 中田慎一郎, 鐘巻将人, Yonghwan Kim, 高田穣.
    • Organizer
      生命科学系学会合同年次大会ConBio2017, 第40回日本分子生物学会年会ワークショップ.
    • Related Report
      2017 Annual Research Report
  • [Presentation] Regulation of homologous recombination by a novel FA protein RFWD3/FANCW.2017

    • Author(s)
      Minoru Takata
    • Organizer
      1st International Symposium on Radiation Therapeutics and Biology (isRTB-2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulation of homologous recombination repair by a novel Fanconi anemia E3 ligase RFWD3/FANCW.2017

    • Author(s)
      Minoru Takata
    • Organizer
      6th US-Japan DNA Repair Meeting, Clark-Kerr Campus, Berkeley, CA, USA.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulation of homologous recombination by a novel FA protein RFWD3.2017

    • Author(s)
      Shojiro Inano, Koichi Sato, Yoko Katsuki, Kerstin Knies, Detlev Schindler, Masamichi Ishiai, Hitoshi Kurumizaka, Minoru Takata.
    • Organizer
      FEBS workshop Nucleotide excision repair and crosslink repair - from molecules to mankind. Smolenice, Slovakia.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A novel Fanconi anemia gene regulates ICL repair and homologous recombination.2016

    • Author(s)
      Minoru Takata
    • Organizer
      第58回日本小児血液・がん学会学術集会 シンポジウム
    • Place of Presentation
      品川プリンスホテル 東京
    • Year and Date
      2016-12-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 相同組換えにおけるRPAおよびRAD51の動態制御はRFWD3によるユビキチン化に依存する2016

    • Author(s)
      稲野将二郎、佐藤浩一、勝木陽子、石合正道、中田慎一郎、胡桃坂仁志、高田 穣
    • Organizer
      第75回日本癌学会学術総会 シンポジウム
    • Place of Presentation
      横浜市パシフィコ横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Novel Fanconi anemia E3 ligase RFWD3 promotes removal of both RPA and RAD51 from DNA damage sites during ICL repair.2016

    • Author(s)
      Shojiro Inano, Koichi Sato, Kerstin Knies, Yoko Katsuki, Shinichiro Nakada, Akifumi Takaori-Kondo, Masamicih Ishiai, Detlev Schindler, Hitoshi Kurumizaka, Minoru Takata.
    • Organizer
      28th Annual Fanconi Anemia research frund Scientific Symposium.
    • Place of Presentation
      Bellevue, WA USA
    • Year and Date
      2016-09-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Myelodysplastic syndrome and acute myeloid leukemia in Japanese Fanconi anemia patients.2016

    • Author(s)
      Miharu Yabe, Tsuyoshi Morimoto, Akiko Fukumura, Keisuke Ohtsubo, Takashi Koike, Takashi Shimizu, Hiromitsu Takakura, Katsuyoshi Koh, Etsuro Ito, Seiji Kojima, Asuka Hira, Minoru Takata and Hiromasa Yabe.
    • Organizer
      28th Annual Fanconi Anemia research frund Scientific Symposium.
    • Place of Presentation
      Bellevue, WA USA
    • Year and Date
      2016-09-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 相同組換えにおけるRPA2のユビキチン化を介した分解2015

    • Author(s)
      稲野将二郎、佐藤浩一、石合正道、勝木陽子、中田慎一郎、胡桃坂仁志、高田 穣
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 複製ストレスによるFANCD2集積部位のゲノムワイド解析2015

    • Author(s)
      石合正道、岩嵜航、高橋数冴、久郷和人、小田有沙、大木千夏、福井哲也、河合秀彦、山本卓、太田邦史、印南秀樹、高田穣
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] UBE2T/FANCT is a novel FA gene identified in Japanese Fanconi anemia patients.2015

    • Author(s)
      Minoru Takata, Asuka Hira, Kenichi Yoshida, Koichi Sato, Akira Shimamoto, Hitoshi Kurumizaka, Seishi Ogawa, Hiromasa Yabe, and Miharu Yabe.
    • Organizer
      The 16th Ataxia-Teleangiectasia Workshop.
    • Place of Presentation
      Beijing China
    • Year and Date
      2015-10-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ファンコニ貧血と遺伝性乳がん卵巣がん:相同組換え欠損を基盤とした高発がん症候群2015

    • Author(s)
      高田 穰
    • Organizer
      第74回日本癌学会 学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] DNA damage and repair in Fanconi anemia2015

    • Author(s)
      Minoru Takata
    • Organizer
      第2回IFOM-京都大学合同シンポジウム
    • Place of Presentation
      京都大学紫蘭会館稲森ホール
    • Year and Date
      2015-10-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia.2015

    • Author(s)
      Hira, K. Yoshida, K.Sato, Y. Shiraishi, K. Chiba, H. Tanaka, S. Miyano, A. Shimamoto, H.Tahara, E.Ito, S.Kojima, H. Kurumizaka, S.Ogawa, M.Takata, H.Yabe, M. Yabe.
    • Organizer
      27th Annual Fanconi anemia research fund Scientific Symposium.
    • Place of Presentation
      Tronto, Canada
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of UBE2T as a novel Fanconi anemia gene.2015

    • Author(s)
      Asuka Hira, Kenichi Yoshida, Koichi Sato, Akita Shimamoto, Hidetoshi Tahara, Hitoshi Kurumizaka, Seishi Ogawa, Minoru Takata, Hiromasa Yabe, Miharu Yabe.
    • Organizer
      ICRR2015
    • Place of Presentation
      Kyoto 国際会館
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Book] 先天性骨髄不全症 診療ガイドライン2017.2017

    • Author(s)
      矢部普正、高田穣、村松秀樹
    • Total Pages
      96
    • Publisher
      診断と治療社
    • ISBN
      9784787823311
    • Related Report
      2017 Annual Research Report
  • [Book] DNA Replication, Recombination, and Repair2015

    • Author(s)
      Masamichi Ishiai, Junya Tomida, Akiko Itaya, James Hejna, Minoru Takata.
    • Total Pages
      35
    • Publisher
      Springer Japan
    • Related Report
      2015 Annual Research Report
  • [Remarks] 京都大学 放射線生物研究センター 晩発効果研究部門 ホームページ

    • URL

      http://www.rbc.kyoto-u.ac.jp/late-effect

    • Related Report
      2017 Annual Research Report
  • [Remarks] 京都大学 放射線生物研究センター 一般の方へ

    • URL

      http://www.rbc.kyoto-u.ac.jp/research

    • Related Report
      2017 Annual Research Report
  • [Remarks] 一般の方へ

    • URL

      http://house.rbc.kyoto-u.ac.jp/research

    • Related Report
      2016 Annual Research Report
  • [Remarks] 放射線生物研究センター

    • URL

      http://www.rbc.kyoto-u.ac.jp

    • Related Report
      2016 Annual Research Report
  • [Remarks] 研究成果アーカイブ

    • URL

      http://house.rbc.kyoto-u.ac.jp/research

    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2022-08-22  

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