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Elucidation of the role of chromatin structure on genome instability using genome editing technique

Research Project

Project/Area Number 25281019
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionOsaka University

Principal Investigator

Fujiwara Tomoko  大阪大学, 医学(系)研究科(研究院), 助教 (70402922)

Co-Investigator(Renkei-kenkyūsha) Todo Takeshi  大阪大学, 大学院医学系研究科, 教授 (90163948)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywordsメダカ / 損傷メモリー / 遺伝的不安定性 / マイクロサテライト不安定性 / 環境ストレス / エピジェネティック変化 / クロマチン構造変化 / ゲノム編集技術
Outline of Final Research Achievements

Genetic instability induced by radiation or chemical mutagens is an interesting phenomenon and plays an important role on carcinogenesis, which appear through long latency period. The factor based under these phenomena is considered to "damage memory", however its entity is not clear. Based on several reports, we hypothesized an epigenetic events such as DNA and histone modification significantly contribute to the "damage memory". In this study, to test the hypothesis we have established a system for detecting the genetic instability. For inducing double strand breaks (DSBs) we used CRISPR, by which we can introduce DSBs at any genomic sequence we want and for the target of genetic instability that on microsatellite was tested. In addition, we have constructed BAC vector containing the entire genome region of ATR or DNA-PKcs gene for the rescue of each mutant, respectively.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (46 results)

All 2016 2015 2014 2013

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (38 results) (of which Int'l Joint Research: 8 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Viable neuronopathic Gaucher disease model in medaka (Oryzias latipes) displays axonal accumulation of alpha-synuclein2015

    • Author(s)
      Norihito Uemura, Masato Koike, Satoshi Ansai, Masato Kinoshita, Tomoko Ishikawa-Fujiwara, Hideaki Matsui, Kiyoshi Naruse, Naoaki Sakamoto, Yasuo Uchiyama, Takeshi Todo, Shunichi Takeda, Hodaka Yamakado, Ryosuke Takahashi
    • Journal Title

      PLoS Genetics

      Volume: 11 Issue: 4 Pages: 1-14

    • DOI

      10.1371/journal.pgen.1005065

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of follicle-stimulating hormone receptor function causes masculinization and sippression of ovarian development in genetically female medaka.2014

    • Author(s)
      Murozumi N, Nakashima R, Hirai T, Kamei Y, Ishikawa-Fujiwara T, Todo T, Kitano T.
    • Journal Title

      Endocrinology

      Volume: 155(8) Issue: 8 Pages: 3136-45

    • DOI

      10.1210/en.2013-2060

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Cryptochrome/Photolyase Family in aquatic organisms.2014

    • Author(s)
      Oliveri P, et al.
    • Journal Title

      Mar Genomics

      Volume: pii: S1874-7787(14) Pages: 22-1

    • DOI

      10.1016/j.margen.2014.02.001

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population.2014

    • Author(s)
      Maruyama H, Yasui T, Ishikawa-Fujiwara T, Morii E, Yamamoto Y, Yoshii T, Takenaka Y, Nakahara S, Todo T, Hongyo T, Inohara H.
    • Journal Title

      Cancer Sci.

      Volume: 105(4) Issue: 4 Pages: 409-417

    • DOI

      10.1111/cas.12369

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] p53-Dependent suppression of genome instability in germ cells.2014

    • Author(s)
      Otozai S, Ishikawa-Fujiwara T, Oda S, Kamei Y, Ryo H, Sato A, Nomura T, Mitani H, Tsujimura T, Inohara H, Todo T.
    • Journal Title

      Mutat Res,

      Volume: 760 Pages: 24-32

    • DOI

      10.1016/j.mrfmmm.2013.12.004

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Circadian and Circalunar Clock Interactions in a Marine Annelid.2013

    • Author(s)
      Zantke J, et al.
    • Journal Title

      Cell Rep.

      Volume: 5(1) Issue: 1 Pages: 99-113

    • DOI

      10.1016/j.celrep.2013.08.031

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish.2013

    • Author(s)
      Ishikawa T, Okada T, Ishikawa-Fujiwara T, Todo T, Kamei Y, Shigenobu S, Tanaka M, Saito TL, Yoshimura J, Morishita S, Toyoda A, Sakaki Y, Taniguchi Y, Takeda S, Mori K.
    • Journal Title

      Mol Biol Cell

      Volume: 24(9) Issue: 9 Pages: 1387-1395

    • DOI

      10.1091/mbc.e12-11-0830

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Targeted Inactivation of Oryzias latipes Rev1 Gene2016

    • Author(s)
      Tomoko I Fujiwara, Yoshihiro Fujikawa, Kumi Nakamura, Takeshi Todo
    • Organizer
      International Meeting on Aquatic Model Organisms for Human Disease and Toxicology Research
    • Place of Presentation
      愛知
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Comprehensive establishment of TLS polymerase mutants using TALENs in Medaka fish.2016

    • Author(s)
      Fujikawa Y, Ishikawa-Fujiawara T, Sakuma T, Yamamoto T, Todo T
    • Organizer
      International Meeting on Aquatic Model Organisms for Human Disease and Toxicology Research
    • Place of Presentation
      愛知
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TALENsを利用したメダカTLSポリメラーゼ遺伝子群変異体の網羅的作製2015

    • Author(s)
      藤川芳宏、藤原(石川)智子、佐久間哲史、山本卓、藤堂剛
    • Organizer
      日本環境変異原学会第44回大会
    • Place of Presentation
      福岡
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] Targeted inactivation of translesion DNA synthesis polymerase genes in Medaka fish using TALENs.2015

    • Author(s)
      Fujikawa Y, Ishikawa-Fujiawara T, Sakuma T, Yamamoto T, Todo T
    • Organizer
      Conference on Transposition and Genome Engineering 2015
    • Place of Presentation
      奈良
    • Year and Date
      2015-11-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Establishment of translesion DNA synthesis polymerase gene mutants in Medaka fish using TALENs.2015

    • Author(s)
      Fujikawa Y, Ishikawa-Fujiawara T, Sakuma T, Yamamoto T, Todo T
    • Organizer
      The 7th Asia and Oceania Conference on Photobiology
    • Place of Presentation
      Taipei
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TALENsによるメダカTLS polymerase 遺伝子破壊2015

    • Author(s)
      藤川芳宏、藤原(石川)智子、佐久間哲史、山本卓、藤堂剛
    • Organizer
      第1回放射線ワークショップ
    • Place of Presentation
      富山
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] ゲノム編集技術を用いた紫外線感受性変異体の作成2015

    • Author(s)
      藤原(石川)智子、藤川芳宏、白石絵吏、藤堂剛
    • Organizer
      第21回小型魚類研究会
    • Place of Presentation
      大阪
    • Year and Date
      2015-09-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] ゲノム編集技術(TALENs)を用いた損傷乗越えDNA合成ポリメラーゼ(Rev3L, Rev)変異体メダカの作製2015

    • Author(s)
      藤川芳宏、藤原(石川)智子、佐久間哲史、山本卓、藤堂剛
    • Organizer
      第21回小型魚類研究会
    • Place of Presentation
      大阪
    • Year and Date
      2015-09-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] メダカにおけるゲノム編集技術(TALENs)を用いた損傷乗り越えDNA合成ポリメラーゼ(Rev3L、Rev7)変異体の作製2015

    • Author(s)
      藤川芳宏、藤原(石川)智子、佐久間哲史、山本卓、藤堂剛
    • Organizer
      変異機構研究会・第28回夏の学校
    • Place of Presentation
      愛知
    • Year and Date
      2015-07-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] モデル生物を使った紫外線感受性解析系の確立2015

    • Author(s)
      藤原(石川)智子
    • Organizer
      第37回日本光医学・光生物学会
    • Place of Presentation
      宮崎
    • Year and Date
      2015-07-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] メダカにおける新規cryptochromeの機能解析2015

    • Author(s)
      藤原(石川)智子、藤川芳宏、白石絵吏、藤堂剛
    • Organizer
      第37回日本光医学・光生物学会
    • Place of Presentation
      宮崎
    • Year and Date
      2015-07-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] ゲノム編集技術TALENを利用したメダカのRev3L, Rev7遺伝子変異体の作製2015

    • Author(s)
      藤川芳宏、藤原(石川)智子、佐久間哲史、山本卓、藤堂剛
    • Organizer
      第37回日本光医学・光生物学会
    • Place of Presentation
      宮崎
    • Year and Date
      2015-07-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] Targeted Inactivation of Rev1 Gene2015

    • Author(s)
      Tomoko I Fujiwara, Yoshihiro Fujikawa, Kumi Nakamura, Takeshi Todo
    • Organizer
      The 15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] p53-Dependent Suppression of Genome Instability in Germ Cells2015

    • Author(s)
      Tomoko Ishikawa-Fujiwara, Shinji Otozai, Shoji Oda, Hiroshi Mitani, Takeshi Todo
    • Organizer
      The 15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Genome Editing in Medaka: Targeted Inactivation of TLS polymerase genes using TALENs.2015

    • Author(s)
      Fujikawa Y, Ishikawa-Fujiawara T, Nakamura K, Sakuma T, Yamamoto T, Todo T
    • Organizer
      The 15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vivo and In vitro Analysis of Testis-ova Formation due to the Irradiation in p53 De¬cient Medaka Testis2015

    • Author(s)
      Kento Nagata, Ayaka Nishitani, Takako Yasuda, Tomomi Asaka, Shoji Oda, Yutaka Suzuki, Tomoko I Fujiwara, Takeshi Todo, Hiroshi Mitani
    • Organizer
      The 15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular mechanism of mutagenesis in Medaka fish2015

    • Author(s)
      Tomoko Ishikawa-Fujiwara, Yoshihiro Fujikawa, Eri Shiraishi, Takeshi Todo
    • Organizer
      International Symposium on Genome Science 2015
    • Place of Presentation
      東京・一橋講堂
    • Year and Date
      2015-01-20 – 2015-01-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] CRISPR/Cas9システムによるメダカ光回復酵素遺伝子変異体の樹立2014

    • Author(s)
      藤原(石川) 智子、藤川 芳宏、藤堂 剛
    • Organizer
      第57回日本放射線影響学会
    • Place of Presentation
      鹿児島・鹿児島県民交流センター
    • Year and Date
      2014-10-01 – 2014-10-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] メダカ生殖細胞における放射線誘発遺伝的不安定性の解析2014

    • Author(s)
      藤原(石川) 智子、音在 信治、尾田 正二、三谷 啓志、猪原 秀典、藤堂 剛
    • Organizer
      第57回日本放射線影響学会
    • Place of Presentation
      鹿児島・鹿児島県民交流センター
    • Year and Date
      2014-10-01 – 2014-10-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] TALENs によるメダカにおける TLS ポリメラーゼ遺伝子群変異体の網羅的作製2014

    • Author(s)
      藤川 芳宏、藤原(石川) 智子、佐久間 哲史、山本 卓、藤堂 剛
    • Organizer
      第57回日本放射線影響学会
    • Place of Presentation
      鹿児島・鹿児島県民交流センター
    • Year and Date
      2014-10-01 – 2014-10-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Functional conversion of (6-4) photolyase and CPD photolyase2014

    • Author(s)
      Daichi Yamada, Junpei Yamamoto, Tomoko Ishikawa, Tomohiro Suzuki, I M. Mahaputra Wijaya, Tatsuya Iwata, Elizabeth D. Getzoff, Takeshi Todo, Shigenori Iwai and Hideki Kandori
    • Organizer
      第52回日本生物物理学会年会
    • Place of Presentation
      北海道・札幌コンベンションセンター
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ゲノム編集技術:CRISPR/Cas9システムによるメダカ光回復酵素遺伝子変異体の樹立2014

    • Author(s)
      藤原(石川) 智子、藤川 芳宏、藤堂 剛
    • Organizer
      第18回日本光生物学協会年会
    • Place of Presentation
      大阪・大阪市立大学学術総合センター
    • Year and Date
      2014-08-22 – 2014-08-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] TALENsを利用した遺伝子破壊によるメダカの損傷乗り越えDNA合成ポリメラーゼ遺伝子変異体の作成2014

    • Author(s)
      藤川 芳宏、藤原(石川) 智子、佐久間 哲史、山本 卓、藤堂 剛
    • Organizer
      第18回日本光生物学協会年会
    • Place of Presentation
      大阪・大阪市立大学学術総合センター
    • Year and Date
      2014-08-22 – 2014-08-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] 変異導入による(6-4)光回復酵素からCPD光回復酵素への機能転換2014

    • Author(s)
      山田 大智、山元 淳平、.I. M. Mahaputra Wijaya、岩田 達也、鈴木智大、石川 智子、Elizabeth D. Getzoff、藤堂 剛、岩井 成憲、神取 秀樹
    • Organizer
      第18回日本光生物学協会年会
    • Place of Presentation
      大阪・大阪市立大学学術総合センター
    • Year and Date
      2014-08-22 – 2014-08-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] CRISPR/Cas9システムによるメダカ光回復酵素遺伝子変異体の樹立2014

    • Author(s)
      藤原(石川) 智子、 藤川 芳宏、 藤堂 剛
    • Organizer
      第36回光医学光生物学会
    • Place of Presentation
      大阪・大阪大学医学部学友会館
    • Year and Date
      2014-07-25 – 2014-07-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] メダカにおけるゲノム編集技術(TALENs)を用いた損傷乗り越えDNA合成ポリメラーゼ遺伝子群変異体の作製2014

    • Author(s)
      藤川 芳宏、藤原(石川) 智子、佐久間 哲史、山本 卓、藤堂 剛
    • Organizer
      第36回光医学光生物学会
    • Place of Presentation
      大阪・大阪大学医学部学友会館
    • Year and Date
      2014-07-25 – 2014-07-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] メダカにおける人工ヌクレアーゼ(TALEN)を用いた損傷乗り越えポリメラーゼ変異体の作製2013

    • Author(s)
      藤川芳宏、藤原(石川)智子、佐久間哲史、山本卓、藤堂剛
    • Organizer
      日本環境変異原学会第42回大会
    • Place of Presentation
      岡山市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Targeted Inactivation of Rev1 gene2013

    • Author(s)
      Tomoko Ishikawa-Fujiwara, Kumi Nakamura, Yoshihiro Fujikawa, Takeshi Todo
    • Organizer
      The 6th Asia and Oceania Conference on Photobiology
    • Place of Presentation
      Sydney, Australia
    • Related Report
      2013 Annual Research Report
  • [Presentation] The molecular structure and damaged-DNA repair activity affected by the chromophore binding2013

    • Author(s)
      Kazunori Zikihara, Kohei Kasakawa, Tomoko Ishikawa, Kristin Tessmar-Raible, Satoru Tokutomi, Takeshi Todo
    • Organizer
      The 6th Asia and Oceania Conference on Photobiology
    • Place of Presentation
      Sydney, Australia
    • Related Report
      2013 Annual Research Report
  • [Presentation] Targeted Inactivation of DNA photolyase family genes using CRISPR system2013

    • Author(s)
      Tomoko Ishikawa-Fujiwara, Kumi Nakamura, Yoshihiro Fujikawa, Takeshi Todo
    • Organizer
      The 6th Asia and Oceania Conference on Photobiology
    • Place of Presentation
      Sydney, Australia
    • Related Report
      2013 Annual Research Report
  • [Presentation] ゲノム編集技術(CRISPR)を利用したメダカ光回復酵素遺伝子変異体の作製2013

    • Author(s)
      藤原 石川 智子、藤川 芳宏、中村 公美、藤堂  剛
    • Organizer
      日本放射線影響学会第56回大会
    • Place of Presentation
      青森市
    • Related Report
      2013 Annual Research Report
  • [Presentation] ゲノム編集技術(TALEN)を用いたメダカにおけるTLS ポリメラーゼ変異体の網羅的作製2013

    • Author(s)
      藤川 芳宏、藤原(石川) 智子、中村 公美、佐久間 哲史、山本  卓、藤堂  剛
    • Organizer
      日本放射線影響学会第56回大会
    • Place of Presentation
      青森市
    • Related Report
      2013 Annual Research Report
  • [Presentation] ゲノム編集技術TALEN を用いた特異的欠損部位変異の作製方法の樹立;メダカRev1 BRCT ドメイン欠損変異体作製2013

    • Author(s)
      中村 公美、藤原(石川) 智子、佐久間 哲史、山本  卓、藤堂  剛
    • Organizer
      日本放射線影響学会第56回大会
    • Place of Presentation
      青森市
    • Related Report
      2013 Annual Research Report
  • [Presentation] DNA-PK 自己リン酸化異常時におけるp53のDSB 修復経路選択への関わり2013

    • Author(s)
      大西 壽子、漆原 佑介、藤原 智子、尾田 正二、藤堂  剛、三谷 啓志
    • Organizer
      日本放射線影響学会第56回大会
    • Place of Presentation
      青森市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Genome editing in medaka: targeted inactivation of DNA photolyase family genes using CRISPR system2013

    • Author(s)
      Tomoko Ishikawa-Fujiwara, Yoshihiro Fujikawa, Kumi Nakamura, Takeshi Todo
    • Organizer
      18th Japanese Medaka and Zebrafish Meeting
    • Place of Presentation
      仙台市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Genome editing in medaka: targeted inactivation of TLS polymerase genes usingTALENs2013

    • Author(s)
      Yoshihiro Fujikawa, Tomoko Ishikawa-Fujiwara, Kumi Nakamura, Tetsushi Sakuma, Takashi Yamamoto, Takeshi Todo
    • Organizer
      18th Japanese Medaka and Zebrafish Meeting
    • Place of Presentation
      仙台市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Genome editing in medaka: targeted inactivation of Rev1 gene by TALEN2013

    • Author(s)
      Kumi Nakamura, Yoshihiro Fujikawa, Tomoko Ishikawa-Fujiwara, Tetsushi Sakuma, Takashi Yamamoto, Takeshi Todo
    • Organizer
      18th Japanese Medaka and Zebrafish Meeting
    • Place of Presentation
      仙台市
    • Related Report
      2013 Annual Research Report
  • [Presentation] ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish2013

    • Author(s)
      Tokiro Ishikawa, Tetsuya Okada, Tomoko Ishikawa-Fujiwara, Takeshi Todo, Yasuhiro Kamei, Shuji Shigenobu, Minoru Tanaka, Taro L. Saito, Jun Yoshimura, Shinichi Morishita, Atsushi Toyoda, Yoshiyuki Sakaki, Yoshihito Taniguchi, Shunichi Takeda, Kazutoshi Mori
    • Organizer
      18th Japanese Medaka and Zebrafish Meeting
    • Place of Presentation
      仙台市
    • Related Report
      2013 Annual Research Report
  • [Book] 光老化科学の最前線 第11章「DNA光化学と概日リズム」2015

    • Author(s)
      藤原(石川)智子、藤堂剛
    • Total Pages
      301
    • Publisher
      シーエムシー出版
    • Related Report
      2015 Annual Research Report

URL: 

Published: 2013-05-21   Modified: 2019-07-29  

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