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出芽酵母Dpb11,RFCの複製モニター機構

Research Project

Project/Area Number 11241205
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNational Institute of Genetics

Principal Investigator

荒木 弘之  国立遺伝学研究所, 細胞遺伝研究系, 教授 (20151160)

Co-Investigator(Kenkyū-buntansha) 杉本 勝則  名古屋大学, 大学院・理学研究科, 助教授 (90192616)
田中 誠司  国立遺伝学研究所, 細胞遺伝研究系, 助手 (50263314)
上村 陽一郎  国立遺伝学研究所, 細胞遺伝研究系, 助手 (20321599)
Project Period (FY) 1999 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥122,900,000 (Direct Cost: ¥122,900,000)
Fiscal Year 2003: ¥33,900,000 (Direct Cost: ¥33,900,000)
Fiscal Year 2002: ¥35,100,000 (Direct Cost: ¥35,100,000)
Fiscal Year 2001: ¥16,100,000 (Direct Cost: ¥16,100,000)
Fiscal Year 2000: ¥25,000,000 (Direct Cost: ¥25,000,000)
Fiscal Year 1999: ¥12,800,000 (Direct Cost: ¥12,800,000)
KeywordsDNA複製 / モニター / チェックポイント / 細胞周期 / ATM / 酵母 / 複製タンパク質 / タンパク質分解 / Cdk / pre-RC / BRCT / 出芽酵母 / 複製因子
Research Abstract

出芽酵母Dpb11とRFC関連の因子の複製モニターにおける機能に関して、本年度は以下のような研究を行った。
1.Dpb11と複合体を形成するSld2は不安定で、S期以外では量が低下する。このSld2の不安定性が、再複製抑制に関与している可能性があるので、触媒する分解系を探したが、既存のユビキチン系の中には存在しなかった。従って、新たな分解系によりSld2量が制御されている可能性がある。
2.Dpb11-Sld2複合体の作用点をピンポイントで決めるため、GINS複合体、Sld3-Cdc45複合体との関連を調べたところ、これら3つの複合体はお互いに依存して複製開始領域に結合することが分かった。従って、Dpb11-Sld2が一群の複製タンパク質が複製開始領域へ結合する過程を制御していることが示唆される。
3.dpb11変異株をG1で停止させ、DNA合成抑制剤であるヒドロキシ尿素存在下にリリースすると複製は開始する。その後、非許容温度下でヒドロキシ尿素からリリースすると複製や細胞分裂は野生株同様に起こるが、細胞の生存率は低下する。この原因を調べたところ、dpb11変異では野生株に比較するとダメージが高い頻度で起こっていることが分かった。従って、dpb11では複製フォークが野生株に比較すると高頻度に崩壊することによりダメージが生じ、修復されないまま細胞分裂を行うため、生存率が低下するものと思われる。
4.ATMの出芽酵母ホモログであるTel1が、2本鎖DNA切断部位に組換えや修復に関与するMre11-Rad50-Xrs2依存的に結合することを明らかにした。

Report

(5 results)
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Takayama, Y: "GINS, a novel multi-protein complex required for chromosomal DNA replication in budding yeast"Genes & Development. 17. 1153-1165 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kubota, Y: "A novel ring-like complex of Xenopus proteins essential for the initiation of DNA replication"Genes & Development. 17. 1141-1152 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iida, T: "Noncompetitive counteractions of DNA polymerase ε and ISW2/yCHRAC for epigenetic inheritance of telomere position effect in Saccharomyces cerevisiae"Molecular and Cellular Biology. 24. 217-227 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakada, D: "ATM-related Tel1 associates with double-strand breaks through an Xrs2-dependent mechanism."Genes & Development. 17. 1957-1962 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Katou, Y: "S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication pausing complex."Nature. 424. 1078-1083 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Naiki, T: "Association of Rad9 with double-strand breaks through a Mec1-dependent mechanism"Molecular and Cellular Biology. 24(印刷中). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakada, Y: "The ATM-related Tel1 protein of Saccharomyces cerevisiae controls a checkpoint response following phleomycin treatment"Nucleic Acids Reserach. 31. 1715-1724 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takayama, Y: "GINS, a novel multi-protein complex required for chromosomal DNA replication in budding yeast"Genes & Development. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kubota, Y: "A novel ring-like complex of Xenopus proteins essential for the initiation of DNA replication"Genes & Development. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wakayama T: "Pie1, a protein interacting with Mec1, controls cell growth and checkpoint responses in Saccharomyces cerevisiae"Molecular and Cellular Biology. 21. 755-764 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Naiki T: "Chl12(Ctf18) forms a novel RFC-related complex and functions redundantly with Rad24 in the DNA replication checkpoint pathway"Molecular and Cellular Biology. 21. 5838-5845 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kamimura Y: "Sld3, which interacts with Cdc45 (Sld4), functions for chromosomal DNA replication in Saccharomyces cerevisiae"The EMBO Journal. 20. 2097-2107 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kondo T: "Recruitment of Mec1 and Ddc1 checkpoint proteins to double-strand breaks through distinct mechanisms"Science. 294. 867-870 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masumoto H: "S-Cdk-dependent phosphorylation of Sld2 essential for chromosomal DNA replication in budding yeast"Nature. 415. 651-655 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hiroshi Masumoto: "Dpb11 controls the association between DNA polymerase α and ε and the autonomously replication sequence region of budding yeast."Molecular and Cellular Biology. 20・8. 2809-2817 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahiro Naiki: "Rfc5, in cooperation with rad24, controls DNA damage checkpoints throughout the cell cycle in Saccharomyces cerevisiae."Molecular and Cellular Biology. 20・16. 5888-5896 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tatsushi Wakayama: "Pie1, a protein interacting with Mec1, controls cell growth and checkpoint responses in Saccharomyces cerevisiae."Molecular and Cellular Biology. 21・3. 755-764 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoichiro Kamimura: "Sld3, which interacts with Cdc45(Sld4), functions for chromosomal DNA replications in Saccharomyces cerevisiae."The EMBO Journal. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoichiro Kamimura: "DNA helicase III of Saccharomyces cerevisiae, encoded by YER176w(HELI), highly unwinds covalently closed, circular DNA in the presence of a DNA topoisomerase and yRF-A."J.Biochem. 25. 236-244 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroshi Masumoto: "Dpb11 controls the association between DNA polymerase α and ε, and the ARS region of budding yeast."Mol.Cell.Biol.. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2018-03-28  

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