• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

How trans-lesion synthesis promote tumorigenesis?

Research Project

Project/Area Number 18K11646
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 63020:Radiation influence-related
Research InstitutionKumamoto University

Principal Investigator

Tateishi Satoshi  熊本大学, 発生医学研究所, 講師 (00227109)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords損傷トレランス / RAD18 / ヒストン / ヒストンメチル化酵素 / ユビキチン / 放射線 / 発癌 / エピジェネティクス / Rad18 / 細胞老化 / UV / 損傷乗越え複製 / ヒストンメチル化修飾 / CRL4Cdt2 / DNAの再複製
Outline of Final Research Achievements

We found that purified human RAD18 / RAD6B complex protein have an activity of mono- and polyubiquitinating histone H2A protein. Irradiation of cells with ionizing radiation increased the ubiquitination level of chromatin protein. The level was reduced in RAD18-deficient cells. RAD18 is thought to ubiquitinate chromatin proteins in response to ionizing radiation. The expression level of histone methyltransferase was decreased in RAD18-deficient cells. It was suggested that RAD18 regulates the expression level of histone methyltransferase. RAD18 is thought to regulate the expression of various genes through histone methylation regulation.

Academic Significance and Societal Importance of the Research Achievements

E3酵素であるRAD18は、DNA複製部位へ集積し損傷乗越え複製を複製停止部位に集積させることで、 損傷乗越え複製を促進する機能をもつ。Rad18欠損マウスは、損傷乗越え複製酵素η欠損マウスと異なる表現型が見られた。RAD18には、損傷乗越え複製の制御とは異なる機序でゲノムを安定化する機構があると推論した。今回の研究で、RAD18は新たにヒストンタンパクのユビキチン化とメチル化に関与していることが示された。RAD18は正常細胞の増殖を維持する一方で、癌化した細胞の増殖も助けてしまう面をもつ。今回の研究成果が、老化の抑制研究または新規の抗癌剤の開発につながることが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (8 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (2 results) Remarks (4 results)

  • [Int'l Joint Research] ノースカロライナ大学(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] ミネソタ大学(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] ノースカロライナ大学チャペルヒル校(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] ノースカロライナ大学チャペルヒル校/病理学部/Cyrus Vaziri 博士(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] RAD18 mediates DNA double-strand break-induced ubiquitination of chromatin protein2021

    • Author(s)
      Mustofa Md Kawsar、Tanoue Yuki、Chirifu Mami、Shimasaki Tatsuya、Tateishi Chie、Nakamura Teruya、Tateishi Satoshi
    • Journal Title

      The Journal of Biochemistry

      Volume: in press Issue: 1 Pages: 33-40

    • DOI

      10.1093/jb/mvab010

    • NAID

      40022722273

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rad18 mediates specific mutational signatures and shapes the genomic landscape of carcinogen-induced tumors in vivo.2021

    • Author(s)
      Lou J, Yang Y, Gu Q, Price BA, Qiu Y, Fedoriw Y, Desai S, Mose LE, Chen B, Tateishi S, Parker JS, Vaziri C, Wu D.
    • Journal Title

      NAR Cancer

      Volume: 3(1) Issue: 1

    • DOI

      10.1093/narcan/zcaa037

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In Silico Drug Repurposing by Structural Alteration after Induced Fit: Discovery of a Candidate Agent for Recovery of Nucleotide Excision Repair in Xeroderma Pigmentosum Group D Mutant (R683W)2021

    • Author(s)
      Takaoka Yutaka、Ohta Mika、Tateishi Satoshi、Sugano Aki、Nakano Eiji、Miura Kenji、Suzuki Takashi、Nishigori Chikako
    • Journal Title

      Biomedicines

      Volume: 9 Issue: 3 Pages: 249-249

    • DOI

      10.3390/biomedicines9030249

    • NAID

      120007026365

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of Chk2/CHEK2 in guarding against environmentally induced DNA damage and replication-stress.2020

    • Author(s)
      Mustofa MK, Tanoue Y, Tateishi C, Vaziri C, Tateishi S.
    • Journal Title

      Environ Mol Mutagen.

      Volume: 61(7) Issue: 7 Pages: 730-735

    • DOI

      10.1002/em.22397

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential roles of Rad18 and Chk2 in genome maintenance and skin carcinogenesis following UV exposure.2018

    • Author(s)
      Tanoue, Y., Toyoda, T., Sun, J, Mustofa, M.K., Tateishi, C., Endo, S., Motoyama, N., Araki, K., Wu, D., Okuno, Y., Tsukamoto, T., Takeya, M., Ihn, H., Vaziri, C., Tateishi, S.
    • Journal Title

      J. Invest. Dermatol.

      Volume: 138 Issue: 12 Pages: 2550-2557

    • DOI

      10.1016/j.jid.2018.05.015

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] DNA repair protein Rad18 restricts LINE-1 mobility2018

    • Author(s)
      Ariumi Yasuo、Kawano Koudai、Yasuda-Inoue Mariko、Kuroki Misao、Fukuda Hiroyuki、Siddiqui Rokeya、Turelli Priscilla、Tateishi Satoshi
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 15894-15894

    • DOI

      10.1038/s41598-018-34288-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diverse roles of RAD18 and Y-family DNA polymerases in tumorigenesis.2018

    • Author(s)
      Yang, Y., Gao, Y., Zlatanou, A., Tateishi, S., Yurchenko, V., Rogozin, I.B., Vaziri, C.
    • Journal Title

      Cell Cycle

      Volume: 17 Issue: 7 Pages: 833-843

    • DOI

      10.1080/15384101.2018.1456296

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] タンパク質のモノユビキチン化2018

    • Author(s)
      立石 智
    • Journal Title

      生体の科学

      Volume: 69 Pages: 123-127

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Possible role of Rad18 in preventing cellular senescence2019

    • Author(s)
      Kawsar Md Mustofa, Satoshi Tateishi
    • Organizer
      日本分子生物学会年会 第42回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Differential roles of Rad18 and Chk2 in genome maintenance and skin carcinogenesis following UV exposure2018

    • Author(s)
      Kawsar Md Mustofa, Yuki Tanoue, Satoshi Tateishi
    • Organizer
      日本分子生物学会年会 第41回大会
    • Related Report
      2018 Research-status Report
  • [Remarks] 熊本大学 発生医学研究所 損傷修復分野 ホームページ

    • URL

      http://www.imeg.kumamoto-u.ac.jp/bunya_top/department_of_cell_maintenance/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 熊本大学 発生医学研究所 損傷修復分野

    • URL

      http://www.imeg.kumamoto-u.ac.jp/bunya_top/department_of_cell_maintenance/

    • Related Report
      2019 Research-status Report
  • [Remarks] Kumamoto Univ. IMEG, Dept. Cell Maintenance

    • URL

      http://www.imeg.kumamoto-u.ac.jp/en/bunya_top/department_of_cell_maintenance/

    • Related Report
      2019 Research-status Report
  • [Remarks]

    • URL

      http://www.imeg.kumamoto-u.ac.jp/bunya_top/department_of_cell_maintenance/

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi