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Elucidation of molecular mechanism of transcription-coupled nucleotide excision repair

Research Project

Project/Area Number 15H02820
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

SAIJO Masafumi  大阪大学, 生命機能研究科, 准教授 (90221986)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywordsヌクレオチド除去修復 / コケイン症候群 / 紫外線高感受性症候群 / ユビキチン化 / SUMO化 / UV / 紫外線 / DNA修復 / ゲノム
Outline of Final Research Achievements

We analyzed transcription-coupled nucleotide excision repair (TC-NER), a subpathway of nucleotide excision repair that rapidly removes transcription-blocking DNA damage, and the following results on the functions of TC-NER factors were obtained. (1) The C-terminal region and SUMOylation of CSB plays critical roles in TC-NER. (2) UVSSA is degraded by proteasome upon dissociation from USP7, resulting in TC - NER deficiency, but when a mutation is introduced at the ubiquitination site, degradation is suppressed and TC - NER becomes normal. (3) Ubiquitination of RNA polymerase II may be involved in the restart of transcription after removal of transcription-blocking DNA damage. These results are important cues to reveal molecular mechanism of TC-NER.

Report

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

    (13 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (5 results) Remarks (1 results)

  • [Int'l Joint Research] フレッド・ハッチンソンがん研究センター/ワシントン大学(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Inhibition of UVSSA ubiquitination suppresses transcription-coupled nucleotide excision repair deficiency caused by dissociation from USP72018

    • Author(s)
      Higa Mitsuru、Tanaka Kiyoji、Saijo Masafumi
    • Journal Title

      The FEBS Journal

      Volume: 285 Issue: 5 Pages: 965-976

    • DOI

      10.1111/febs.14382

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of splice switching oligonucleotides targeting the Cockayne syndrome group B gene product in order to change the diseased cell state.2018

    • Author(s)
      Sin Yoosil、Makimura Futaba、 Saijo Masafumi、Obika Satoshi
    • Journal Title

      Biochemical and Biophysicai Research Communications

      Volume: ー

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DGCR8 Mediates Repair of UV-Induced DNA Damage Independently of RNA Processing.2017

    • Author(s)
      Philamer C. Calses, Kiranjit K. Dhillon, Nyka Tucker, Yong Chi, Jen-wei Huang, Masaoki Kawasumi, Paul Nghiem, Yemin Wang, Bruce E. Clurman, Celine Jacquemont, Philip R. Gafken, Kaoru Sugasawa, Masafumi Saijo, Toshiyasu Taniguchi
    • Journal Title

      Cell Reports

      Volume: 19 Issue: 1 Pages: 162-174

    • DOI

      10.1016/j.celrep.2017.03.021

    • NAID

      120006360182

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stabilization of Ultraviolet (UV)-stimulated Scaffold Protein A by Interaction with Ubiquitin-specific Peptidase 7 Is Essential for Transcription-coupled Nucleotide Excision Repair.2016

    • Author(s)
      Mitsuru Higa, Xue Zhang, Kiyoji Tanaka, Masafumi Saijo
    • Journal Title

      Journal of Biological Chemistry

      Volume: 291 Issue: 26 Pages: 13771-13779

    • DOI

      10.1074/jbc.m116.724658

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The C-terminal Region and SUMOylation of Cockayne Syndrome Group B Protein Play Critical Roles in Transcription-coupled Nucleotide Excision Repair.2016

    • Author(s)
      Yooksil Sin,Kiyoji Tanaka, Masafumi Saijo
    • Journal Title

      Journal of Biological Chemistry

      Volume: 291 Issue: 3 Pages: 1387-1397

    • DOI

      10.1074/jbc.m115.683235

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Regulation of Transcription Elongation by the XPG-TFIIH Complex Is Implicated in Cockayne Syndrome.2015

    • Author(s)
      Takashi Narita, Keiko Narita, Arato Takedachi, Masafumi Saijo, Kiyoji Tanaka
    • Journal Title

      Molecular and Cellular Biology

      Volume: 35 Issue: 18 Pages: 3178-3188

    • DOI

      10.1128/mcb.01401-14

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 転写を阻害するDNA損傷を除去する仕組み:転写と共役したヌクレオチド除去修復に関与する因子の機能解析2018

    • Author(s)
      西條将文
    • Organizer
      第6回 バイオシグナル研究会(神戸大学)
    • Related Report
      2017 Annual Research Report
  • [Presentation] UVSSAユビキチン化の阻害はUSP7からの解離で引き起こされた転写と共役したヌクレオチド除去修復の欠損を抑制する2017

    • Author(s)
      比嘉光、田中亀代次、西條将文
    • Organizer
      第40回 日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] USP7との結合によるUVSSAの安定性は転写と共役したヌクレオチド除去修復において必須である2016

    • Author(s)
      比嘉光、Zhang Xue、田中亀代次、西條将文
    • Organizer
      第39回日本分子生物学会年会
    • 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
  • [Presentation] 紫外線DNA損傷とSUMO-Ubi系、そして病態2016

    • Author(s)
      西條 将文
    • Organizer
      第13回SUMO研究会
    • Place of Presentation
      関西学院大学大阪梅田キャンパス(大阪府大阪市)
    • Year and Date
      2016-01-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] 転写と共役した修復におけるCSBタンパク質の機能にはC末端領域とSUMO化が必要である2015

    • Author(s)
      申 育實、田中 亀代次、西條 将文
    • Organizer
      BMB2015(第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会)
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Remarks] 大阪大学生命機能研究科研究室ホームページ

    • URL

      http://www.fbs.osaka-u.ac.jp/jpn/general/lab/12/

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report

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Published: 2015-04-16   Modified: 2022-08-25  

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