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Genome-wide analysis of cooperative action among DNA polymerases

Research Project

Project/Area Number 16H06151
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Genome biology
Research InstitutionTohoku University

Principal Investigator

Daigaku Yasukazu  東北大学, 学際科学フロンティア研究所, 助教 (80619875)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥27,430,000 (Direct Cost: ¥21,100,000、Indirect Cost: ¥6,330,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2017: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2016: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
KeywordsDNA複製 / 突然変異 / DNAポリメラーゼ / ゲノム安定性 / DNAポリメラーゼ / DNA複製 / ゲノムワイド解析
Outline of Final Research Achievements

There are more than 10 DNA polymerases encoded in eukaryotic cells and two polymerases (Polδ and Polε) replicate the bulk of parental DNA. On the other hand, some of other polymerases are less processive but tolerant replication blockage. However, we know little about how activities of these DNA polymerases are coordinated during genome replication. We first tackled this issue in fission yeast using the experimental system to examine genome-wide usage of DNA polymerases (Pu-seq). We then applied this system to C. elegans and human culture cells to investigate flexibility in the mechanism of replication during change in cell identity such as differentiation and tumorigenesis.

Academic Significance and Societal Importance of the Research Achievements

現在までに,ヒトを含めた多細胞生物では老化,がん化という細胞の変遷がゲノム情報の安定性へ影響することが示されてきた.がん細胞ではポリメラーゼ遺伝子に多くの変異が見つかるなど,その機能不全とがんにおけるゲノム不安定性との関連性が示唆され,同様に,老化した細胞においても複製ストレスを示すバイオマーカーが観察される.その過程でのDNA複製機構に起きる変遷を具体的に示す研究成果は乏しい状況であったが,本研究で開発された実験系を応用することにより,発がんや老化へ寄与する仕組みの解明へと大きく前進すると期待される.

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (18 results)

All 2020 2019 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (14 results) (of which Int'l Joint Research: 4 results,  Invited: 6 results)

  • [Journal Article] Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled Repair2020

    • Author(s)
      Nakazawa Y, Hara Y, Oka Y, Komine O, van den Heuvel D, Guo C, Daigaku Y, Isono M, He Y, Shimada M, Kato K, Jia N, Hashimoto S, Kotani Y, Miyoshi Y, Tanaka M, Sobue A, Mitsutake N, Suganami T, Masuda A, Ohno K, Nakada S, Mashimo T, Yamanaka K, Luijsterburg MS, Ogi T
    • Journal Title

      Cell

      Volume: 19 Issue: 6 Pages: 1228-1244

    • DOI

      10.1016/j.cell.2020.02.010

    • NAID

      120006871293

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Vital roles of PCNA K165 modification during C. elegans gametogenesis and embryogenesis2019

    • Author(s)
      Shao Zhenhua、Niwa Shinsuke、Higashitani Atsushi、Daigaku Yasukazu
    • Journal Title

      DNA Repair

      Volume: 82 Pages: 102688-102688

    • DOI

      10.1016/j.dnarep.2019.102688

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spatial separation between replisome‐ and template‐induced replication stress signaling2018

    • Author(s)
      Garcia‐Rodriguez Nrstor、Morawska Magdalena、Wong Ronald P、Daigaku Yasukazu、Ulrich Helle D
    • Journal Title

      The EMBO Journal

      Volume: 37 Issue: 9

    • DOI

      10.15252/embj.201798369

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PCNA ubiquitylation ensures timely completion of unperturbed DNA replication in fission yeast.2017

    • Author(s)
      Daigaku Y, Etheridge TJ, Nakazawa Y, Nakayama M, Watson AT, Miyabe I, Ogi T, Osborne MA, Carr AM.
    • Journal Title

      PLoS Genetics

      Volume: 13 Issue: 5 Pages: e1006789-e1006789

    • DOI

      10.1371/journal.pgen.1006789

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Global usage of replicative DNA polymerase in human cells2019

    • Author(s)
      Fumiya Yoshifuji, Eri Koyanagii, Tomoo Ogi, Toyoaki Natsume, Masato Kanemaki, Yasukazu Daigaku
    • Organizer
      Cold Spring Harbor Laboratory Meeting "Eukaryotic DNA Replication & Genome Maintenance"
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DNAポリメラーゼ合成プロファイルを用いたヒト細胞における複製開始反応の定量的解析2019

    • Author(s)
      吉藤郁弥,小柳恵理,荻朋男,夏目豊彰,鐘巻将人,大学保一
    • Organizer
      日本遺伝学会91回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] DNAポリメラーゼ機能から見るヒト細胞でのゲノム複製機構2019

    • Author(s)
      小柳恵理,吉藤郁弥,荻朋男,夏目豊彰,鐘巻将人,大学保一
    • Organizer
      第25回DNA複製・組換え・修復ワークショップ
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト細胞のおけるDNA複製動態の柔軟さ,危うさ2019

    • Author(s)
      小柳恵理,吉藤郁弥,大学保一
    • Organizer
      第42回分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] DNAポリメラーゼ機能のゲノムプロファイルから見る染色体複製システム2019

    • Author(s)
      小柳恵理,吉藤郁弥,荻朋男,夏目豊彰,鐘巻将人,大学保一
    • Organizer
      第37回染色体ワークショップ
    • Related Report
      2019 Annual Research Report
  • [Presentation] 分裂酵母の複製フォークの動態から見る複製開始反応の確率的現象2018

    • Author(s)
      大学保一
    • Organizer
      日本遺伝学会第90回大会
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Invited
  • [Presentation] Usage of error prone DNA polymerase during genome replication2018

    • Author(s)
      Mayumi Nakayama, Ryoko Omi, Yasukazu Daigaku
    • Organizer
      11th 3R+3C Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ゲノム科学的視点から見るDNAポリメラーゼ機能の柔軟性2018

    • Author(s)
      大学保一、中山真由美
    • Organizer
      第41回分子生物学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 複製フォーク動態のゲノム科学的解析から見る染色体複製2018

    • Author(s)
      大学保一、吉藤郁弥、邵 震華
    • Organizer
      第36回染色体ワークショップ
    • Related Report
      2018 Annual Research Report
  • [Presentation] 染色体構造とDNA複製動態 -分裂酵母とヒト細胞の視点から-2018

    • Author(s)
      大学保一
    • Organizer
      染色体研究の最前線
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] DNA polymerase usage and mutagenesis2018

    • Author(s)
      Yasukazu Daigaku
    • Organizer
      JSPS-DST Japan-India Forum for Advanced Study: Epigenetics and Human Disease
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Usage of error prone DNA polymerase during genome replication2018

    • Author(s)
      大学保一
    • Organizer
      11th 3R+3C Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 複製クランプのユビキチ化によるDNA複製機構の メンテナス2016

    • Author(s)
      大学保一
    • Organizer
      日本遺伝学会第88回大会 プレナリーワークショップ
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 複製クランプPCNAの分子修飾のゲノム複製における役割2016

    • Author(s)
      大学保一
    • Organizer
      第39回日本分子生物学会年会
    • Related Report
      2016 Annual Research Report
    • Invited

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Published: 2016-04-21   Modified: 2021-02-19  

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