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Function of MLL fusion partner ENL in DSB repair

Research Project

Project/Area Number 26740016
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Risk sciences of radiation and chemicals
Research InstitutionTokyo University of Technology (2016)
St. Marianna University School of Medicine (2014-2015)

Principal Investigator

UI Ayako  東京工科大学, 応用生物学部, 准教授 (00469967)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsDNA修復 / 転写 / ポリコーム / ENL / ATM / がん / MLLT1 / Polycomb / ゲノム安定性 / DSB / PRC1 / ユビキチン
Outline of Final Research Achievements

ENL (MLLT1), a factor of Super Elongation Complex (SEC) and fusion partner of the Mixed-Lineage-Leukemia (MLL) protein, activates transcription. Here we found that ENL interacts with BMI1/RING1B, the E3-ubiquitin-ligase of PRC1 (Polycomb Repressive Complex 1). After DSB, ENL is phosphorylated by ATM at its well-conserved SQ-sites and increase its interaction with BMI1. Then, ENL recruits Polycomb at transcription sites near DSBs to repress transcription by promoting ubiquitination of H2A. Furthermore, the function of ENL is required for the recruitment of DSB repair proteins at DSB sites near transcription sites and DSB repair. These results suggest that under the control of ATM, ENL recruits PRC1 at transcriptional elongation sites to repress transcription and promotes DSB repair. This mechanism ensures a rapid and systematic transcriptional repression by DSBs to secure cellular homeostasis and genome integrity.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (20 results)

All 2017 2016 2015 2014

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (17 results) (of which Int'l Joint Research: 1 results,  Invited: 7 results)

  • [Journal Article] Collaboration of MLLT1/ENL, Polycomb and ATM for transcription and genome integrity2016

    • Author(s)
      Ui A and Yasui A
    • Journal Title

      Nucleus

      Volume: 7 Issue: 2 Pages: 138-145

    • DOI

      10.1080/19491034.2016.1177681

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Transcriptional elongation factor ENL phosphorylated by ATM recruits polycomb and switches off transcription for DSB repair2015

    • Author(s)
      Ui A, Nagaura Y, Yasui A
    • Journal Title

      Molecular Cell

      Volume: 58 Issue: 3 Pages: 468-482

    • DOI

      10.1016/j.molcel.2015.03.023

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Transcriptional Elongation Factor ENL Phosphorylated by ATM Recruits Polycomb and Switches Off Transcription for DSB Repair2015

    • Author(s)
      Ayako Ui, Yuko Nagaura, Akira Yasui
    • Journal Title

      Molecular Cell

      Volume: in press

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 新規Ubiquitin E3-ligaseのDSB修復を介した染色体安定機構2017

    • Author(s)
      宇井彩子
    • Organizer
      染色体ワークショップ
    • Place of Presentation
      かずさアカデミアホール(千葉県木更津市)
    • Year and Date
      2017-01-11
    • Related Report
      2016 Annual Research Report
  • [Presentation] DSB修復に関与する新規Ubiquitin E3-ligaseの機能解析2016

    • Author(s)
      宇井彩子
    • Organizer
      パシフィコ横浜(神奈川県横浜市)
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Chromatin remodeling complexes belonging to ISWI and SWI/SNF families cooperatively promote DSB repair to prevent genome instability.2016

    • Author(s)
      宇井彩子
    • Organizer
      3R symposium
    • Place of Presentation
      ホテル一畑(島根県松江市)
    • Year and Date
      2016-11-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DSB修復に関与する新規Ubiquitin E3-ligaseの機能解析2016

    • Author(s)
      宇井彩子
    • Organizer
      生物ゲノム安定維持の分子機構
    • Place of Presentation
      国立遺伝学研究所(静岡県三島市)
    • Year and Date
      2016-10-24
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] DNA損傷修復と転写の共役機構と染色体安定性2016

    • Author(s)
      宇井彩子
    • Organizer
      第9回Symphony
    • Place of Presentation
      ホテルメトロポリタンエドモンド(東京都千代田区)
    • Year and Date
      2016-09-18
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] エストロゲン依存的なユビキチン化制御機構の解2016

    • Author(s)
      宇井彩子
    • Organizer
      第2回Neo Vitamin D Workshop 学術集会
    • Place of Presentation
      TKPガーデンシティ品川(東京都品川区)
    • Year and Date
      2016-08-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] ATMによる転写とDSB修復の制御2016

    • Author(s)
      宇井彩子
    • Organizer
      転写サイクル「冬の若手ワークショップ2016」
    • Place of Presentation
      山梨県南都留郡 ホテルマウント富士入口
    • Year and Date
      2016-02-04
    • Related Report
      2015 Research-status Report
  • [Presentation] ATMによる転写とDSB修復の制御2016

    • Author(s)
      宇井彩子
    • Organizer
      染色体ワークショップ
    • Place of Presentation
      宮城県仙台市 松島一の坊
    • Year and Date
      2016-01-12
    • Related Report
      2015 Research-status Report
  • [Presentation] ユビキチンを介したDSB依存的な転写と修復の共役機構2015

    • Author(s)
      宇井彩子
    • Organizer
      新学術領域研究領域「ユビキチンネオバイオロジー」平成27年度領域班会議
    • Place of Presentation
      千葉県南房総市 富浦ロイヤルホテル
    • Year and Date
      2015-12-19
    • Related Report
      2015 Research-status Report
  • [Presentation] ATMによる転写とDSB修復の制御2015

    • Author(s)
      宇井彩子
    • Organizer
      放射線医学総合研究所セミナー
    • Place of Presentation
      千葉県千葉市 放射線医学総合研究所
    • Year and Date
      2015-12-18
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] ATMは転写部位の近傍でDSBが生じると、転写促進因子のENLをリン酸化して、転写抑制因子のポリコームを呼び込み、転写を抑制する2015

    • Author(s)
      宇井彩子
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      兵庫県神戸市 ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] ATMは転写因子をリン酸化し、制御することにより、転写を抑制し、DSB修復を促進する2015

    • Author(s)
      宇井彩子
    • 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 Research-status Report
  • [Presentation] Phosphorylation of transcriptional elongation factor ENL by ATM turns off the transcription by recruiting Polycomb for DSB repair2015

    • Author(s)
      Ayako Ui
    • Organizer
      第74回日本癌学会
    • Place of Presentation
      愛知県名古屋市 名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] DSB修復と転写におけるヒストン修飾とクロマチンリモデリング2015

    • Author(s)
      宇井彩子
    • Organizer
      遺伝研研究会
    • Place of Presentation
      静岡県三島市 国立遺伝研究所
    • Year and Date
      2015-10-01
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] ATMは、転写因子ENL/MLLT1とPolycombに作用して、DSB近傍の転写とDSB修復を制御する2014

    • Author(s)
      宇井彩子、永浦裕子、安井明
    • Organizer
      染色体ワークショップ
    • Place of Presentation
      安芸グランドホテル (広島県 廿日市市)
    • Year and Date
      2014-12-15 – 2014-12-17
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] DSBに応答して、ENL/MLLT1はPolycombと共に転写の抑制を制御する2014

    • Author(s)
      宇井彩子、永浦裕子、安井明
    • Organizer
      分子生物学会
    • Place of Presentation
      パシフィコ横浜 (神奈川県 横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] ATM は転写因子Polycomb とENL/MLT1 に作用 してDSB 近傍の転写とDSB 修復を制御する2014

    • Author(s)
      宇井彩子、永浦裕子、安井明
    • Organizer
      遺伝研集会
    • Place of Presentation
      国立遺伝研究所(静岡県 三島市)
    • Year and Date
      2014-11-06 – 2014-11-07
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-04-04   Modified: 2018-03-22  

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