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In vitro analysis of functions of cohesin in replication-coupled sister-chromatid cohesion and DNA double-strand break repair

Research Project

Project/Area Number 25711022
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Genetics/Chromosome dynamics
Research InstitutionKyushu University (2016)
Osaka University (2013-2015)

Principal Investigator

Takahashi Tatsuro  九州大学, 理学(系)研究科(研究院), 准教授 (50452420)

Research Collaborator HIGASHI Torahiko  
KAWASOE Yoshitaka  
YAMAGUCHI Yohko  
TERUI Riki  
HAYASHI Sae  
KAYUKAWA Taiki  
ODA Satomi  
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥26,260,000 (Direct Cost: ¥20,200,000、Indirect Cost: ¥6,060,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2015: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2013: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
KeywordsDNA複製 / 染色体接着 / 相同組換え / 二重鎖切断 / ツメガエル卵抽出液 / コヒーシン / アセチル化 / 姉妹染色体接着 / DNA二重鎖切断 / DNA損傷修復 / ツメガエル / 染色体分配 / DNA修復 / 無細胞系
Outline of Final Research Achievements

Sister-chromatid cohesion, mediated by the cohesin complex, facilitates precise segregation of sister chromosomes at M-phase and promotes repair of DNA double-strand breaks (DSBs). However, how cohesin promotes those reactions has not been clearly understood. Using Xenopus egg extracts and biochemical reconstitution with purified proteins as model systems, we revealed functional relationship between XEco2 cohesin acetyltransferase, a key enzyme in the cohesion establishment reaction, and multiple replication proteins. We also constructed in vitro model systems for post-replicative DSB repair, and analyzed involvement of cohesin in the repair reaction. This study clarified novel functional interaction between sister-chromatid cohesion and DNA replication.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (37 results)

All 2017 2016 2015 2014 2013 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (31 results) (of which Int'l Joint Research: 3 results,  Invited: 9 results)

  • [Journal Article] MutSα maintains the mismatch repair capability by inhibiting PCNA unloading2016

    • Author(s)
      Kawasoe, Y., Tsurimoto, T., Nakagawa, T., Masukata, H., Takahashi, TS.
    • Journal Title

      eLIFE

      Volume: 12;5

    • DOI

      10.7554/elife.15155

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] PCNA Retention on DNA into G2/M Phase Causes Genome Instability in Cells Lacking Elg12016

    • Author(s)
      Catherine Johnson, Vamsi K. Gali, Tatsuro S. Takahashi, Takashi Kubota
    • Journal Title

      Cell Reports

      Volume: 16 Issue: 3 Pages: 684-695

    • DOI

      10.1016/j.celrep.2016.06.030

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reconstitution of mitotic chromatids with a minimum set of purified factors2015

    • Author(s)
      Keishi Shintomi, Tatsuro S. Takahashi, and Tatsuya Hirano
    • Journal Title

      Nature Cell Biology

      Volume: 17 Issue: 8 Pages: 1014-1023

    • DOI

      10.1038/ncb3187

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] RecQ4 promotes the conversion of the pre-initiation complex at a site-specific origin for DNA unwinding in Xenopus egg extracts2015

    • Author(s)
      Sanuki, Kubota, Kanemaki MT, Takahashi TS, Mimura S, Takisawa H
    • Journal Title

      Cell Cycle

      Volume: 14-7 Issue: 7 Pages: 1010-23

    • DOI

      10.1080/15384101.2015.1007003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thymine DNA glycosylase is a CRL4Cdt2 substrate.2014

    • Author(s)
      Slenn TJ, Morris B, Havens CG, Freeman RM Jr, Takahashi TS, Walter JC.
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 289 Issue: 33 Pages: 23043-55

    • DOI

      10.1074/jbc.m114.574194

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MutS stimulates the endonuclease activity of MutL in an ATP-hydrolysis-dependent manner.2013

    • Author(s)
      Shimada, A., Kawasoe, Y., Hata, Y., Takahashi, T.S., Masui, R., Kuramitsu, S., Fukui, K.
    • Journal Title

      FEBS Journal

      Volume: 280 (14) Issue: 14 Pages: 3467-3479

    • DOI

      10.1111/febs.12344

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] ミスマッチ修復依存的なヘテロ二重鎖解消反応の試験管内解析2017

    • Author(s)
      高橋達郎
    • Organizer
      第34回染色体ワークショップ・第15回核ダイナミクス研究会
    • Place of Presentation
      千葉県木更津市
    • Year and Date
      2017-01-11
    • Related Report
      2016 Annual Research Report
  • [Presentation] In vitro analysis of interplay between chromatin replication, homology-directed repair, and mismatch repair2016

    • Author(s)
      高橋達郎
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Interplay between DNA synthesis, chromatin assembly, and mismatch repair2016

    • Author(s)
      高橋達郎
    • Organizer
      The 10th 3R symposium
    • Place of Presentation
      島根県松江市
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chromatin remodeling facilitates eukaryotic mismatch repair by promoting the displacement of nucleosomes around mismatches2016

    • Author(s)
      高橋達郎
    • Organizer
      At the Intersection of DNA Replication and Genome Maintenance: from Mechanisms to Therapy
    • Place of Presentation
      Trieste, Italy
    • Year and Date
      2016-06-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] コヒーシンが複製後のDSB修復に機能する機構の新規試験管内系による解析2015

    • Author(s)
      粥川太貴
    • Organizer
      第38回日本分子生物学会年会 第88回日本生化学会 合同年会
    • Place of Presentation
      兵庫県神戸市 神戸国際会議場
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] MutSα⁄β依存的にDNAに呼び込まれる新規ミスマッチ修復関連因子2015

    • Author(s)
      織田里美
    • Organizer
      第38回日本分子生物学会年会 第88回日本生化学会 合同年会
    • Place of Presentation
      兵庫県神戸市 神戸国際会議場
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] DNA複製とミスマッチ修復の機能的相関2015

    • Author(s)
      高橋達郎
    • Organizer
      第38回日本分子生物学会年会 第88回日本生化学会 合同年会
    • Place of Presentation
      兵庫県神戸市 神戸国際会議場
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] XEco2はMcm2-7と相互作用しDNA複製に依存したSororin染色体結合反応に機能する2015

    • Author(s)
      高橋達郎
    • Organizer
      第23回DNA複製・組換え・修復ワークショップ
    • Place of Presentation
      静岡県焼津市 焼津グランドホテル
    • Year and Date
      2015-10-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] ミスマッチ修復因子MutSαは PCNAのDNAからの解離を阻害して修復の鎖特異性を保持する2015

    • Author(s)
      河添好孝
    • Organizer
      第23回DNA複製・組換え・修復ワークショップ
    • Place of Presentation
      静岡県焼津市 焼津グランドホテル
    • Year and Date
      2015-10-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] 染色体複製と協調して機能する遺伝情報維持機構2015

    • Author(s)
      高橋達郎
    • Organizer
      国立遺伝学研究所・研究集会「染色体DNAの安定維持の分子メカニズム」
    • Place of Presentation
      静岡県三島市 国立遺伝学研究所
    • Year and Date
      2015-10-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] The mechanism of the MutSα-dependent strand memory reaction in Xenopus egg extract2015

    • Author(s)
      高橋達郎
    • Organizer
      Cold Spring Harbor Laboratory Meeting "Eukaryotic DNA replication & Genome Maintenance"
    • Place of Presentation
      Cold Spring Harbor, NY, USA
    • Year and Date
      2015-09-01
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] クロマチン複製とDNAミスマッチ修復の機能的相関2015

    • Author(s)
      高橋達郎
    • Organizer
      第9回日本エピジェネティクス研究会年会
    • Place of Presentation
      東京一ツ橋学術総合センター
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] PCNAとXEco2はDNA複製と協調したSororin染色体結合反応に機能する2014

    • Author(s)
      高橋 達郎
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      神奈川県横浜市 パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] スマッチ修復因子MutSαはPCNAのDNAからの解離を阻害することで新生鎖の記憶を保持する2014

    • Author(s)
      河添 好孝
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      神奈川県横浜市 パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] MutSα依存的なミスマッチ塩基対周辺のヌクレオソーム排除反応2014

    • Author(s)
      照井 利輝
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      神奈川県横浜市 パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] MutSα-dependent exclusion of nucleosomes from mismatch sites in Xenopus egg extracts2014

    • Author(s)
      高橋 達郎
    • Organizer
      The 9th 3R Symposium
    • Place of Presentation
      静岡県御殿場市 ホテル時之栖
    • Year and Date
      2014-11-17 – 2014-11-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] PCNA and XEco2 couple chromatin loading of Sororin to DNA replication in Xenopus egg extracts2014

    • Author(s)
      東 寅彦
    • Organizer
      The 9th 3R Symposium
    • Place of Presentation
      静岡県御殿場市 ホテル時之栖
    • Year and Date
      2014-11-17 – 2014-11-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] MutSα prevents dissociation of PCNA from DNA to keep strand information for eukaryotic mismatch repair2014

    • Author(s)
      河添 好孝
    • Organizer
      The 9th 3R Symposium
    • Place of Presentation
      静岡県御殿場市 ホテル時之栖
    • Year and Date
      2014-11-17 – 2014-11-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] MutSα prevents PCNA unloading to keep strand information for eukaryotic mismatch repair2014

    • Author(s)
      高橋 達郎
    • Organizer
      国立遺伝学研究所・研究集会「染色体 DNA の安定維持の分子メカニズム」
    • Place of Presentation
      静岡県三島市 国立遺伝学研究所
    • Year and Date
      2014-11-06 – 2014-11-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] MutSα prevents dissociation of PCNA from DNA to keep strand information for eukaryotic mismatch repair2014

    • Author(s)
      高橋 達郎
    • Organizer
      The 5th US-Japan DNA repair meeting
    • Place of Presentation
      徳島県鳴門市 グランドエクシブ鳴門
    • Year and Date
      2014-10-28 – 2014-10-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] ミスマッチ修復とクロマチン複製のカップリング2014

    • Author(s)
      高橋 達郎
    • Organizer
      蛋白研セミナー 『染色体伝承の分子背景:複製から染色体分離まで』
    • Place of Presentation
      大阪府吹田市 大阪大学蛋白質研究所 1 階講堂
    • Year and Date
      2014-09-25 – 2014-09-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 真核生物ミスマッチ修復機構とクロマチン動態、DNA損傷応答機構のクロストーク2014

    • Author(s)
      高橋達郎
    • Organizer
      平成25年度「がん研究分野の特性等を踏まえた支援活動」 公開シンポジウム
    • Place of Presentation
      東京都千代田区 学術総合センター
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] MutSα-dependent eviction of nucleosomes around mismatch sites in Xenopus egg extracts2014

    • Author(s)
      Tatsuro Takahashi, Riki Terui, Kanae Taki, Koji Nagao, Takuro Nakagawa, Uimiko Kubota, Haruhiko Takisawa, Chikashi Obuse, Hisao Masukata
    • Organizer
      International Conference: Replication, repair, and transcription; coupling mechanisms and chromatin dynamics for genome integrity
    • Place of Presentation
      京都市左京区 京都大学 時計台100周年記念ホール
    • Related Report
      2013 Annual Research Report
  • [Presentation] Evidence that DNA-loaded PCNA acts as the strand marker for eukaryotic mismatch repair2013

    • Author(s)
      Yoshitaka Kawasoe, Toshiki Tsurimoto,Takuro Nakagawa, Hisao Masukata, Tatsuro Takahashi
    • Organizer
      Cold Spring Harbor Laboratory Meeting "Eukaryotic DNA replication & Genome Maintenance"
    • Place of Presentation
      Cold Spring Harbor, NY
    • Related Report
      2013 Annual Research Report
  • [Presentation] MutSα-dependent eviction of nucleosomes around mismatch sites in Xenopus egg extracts2013

    • Author(s)
      Riki Terui, Kanae Taki, Torahiko Higashi, Takuro Nakagawa, Hisao Masukata, Tatsuro Takahashi
    • Organizer
      Cold Spring Harbor Laboratory Meeting "Eukaryotic DNA replication & Genome Maintenance"
    • Place of Presentation
      Cold Spring Harbor, NY
    • Related Report
      2013 Annual Research Report
  • [Presentation] Essential roles of the N-terminal region of XEco2 acetyltransferase for cohesion establishment in Xenopus egg extracts2013

    • Author(s)
      Torahiko Higashi, Takuro Nakagawa, Hisao Masukata, Tatsuro Takahashi
    • Organizer
      Cold Spring Harbor Laboratory Meeting "Eukaryotic DNA replication & Genome Maintenance"
    • Place of Presentation
      Cold Spring Harbor, NY
    • Related Report
      2013 Annual Research Report
  • [Presentation] MutSα-dependent eviction of nucleosomes around mismatch sites in Xenopus egg extracts2013

    • Author(s)
      Tatsuro Takahashi, Riki Terui, Kanae Taki, Koji Nagao, Takuro Nakagawa, Uimiko Kubota, Haruhiko Takisawa, Chikashi Obuse, Hisao Masukata
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      兵庫県神戸市 神戸国際会議場
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ミスマッチ周辺でのMutS依存的ヌクレオソーム除去反応に関わる因子の探索2013

    • Author(s)
      Riki Terui, Kanae Taki, koji Nagao, Takuro Nakagawa, Yumiko Kubota, Haruhiko Takisawa, Chikashi Obuse, Hisao Masukata
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      兵庫県神戸市 神戸国際会議場
    • Related Report
      2013 Annual Research Report
  • [Presentation] ミスマッチ修復機構がクロマチン複製の場で機能するための機構2013

    • Author(s)
      高橋達郎
    • Organizer
      国立遺伝学研究所・研究会「染色体 DNA の安定維持の分子メカニズム」
    • Place of Presentation
      静岡県三島市 国立遺伝学研究所
    • Related Report
      2013 Annual Research Report
  • [Presentation] ミスマッチ修復機構がクロマチン複製の場で機能するための機構2013

    • Author(s)
      高橋達郎
    • Organizer
      国立遺伝学研究所・研究会「クロマチンによる遺伝情報のエピジェネティック制御機構」
    • Place of Presentation
      静岡県三島市 国立遺伝学研究所
    • Related Report
      2013 Annual Research Report
  • [Presentation] Coupling of cohesin acetylation to the process of DNA replication in Xenopus egg extracts

    • Author(s)
      Torahiko Higashi, Takuro Nakagawa, Hisao Masukata, Tatsuro Takahashi
    • Organizer
      The 18th IMCB Symposium
    • Place of Presentation
      東京都文京区 東京大学弥生講堂
    • Related Report
      2013 Annual Research Report
    • Invited

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

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