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Regulation of initiation and elongation stages of DNA replication

Research Project

Project/Area Number 13043029
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionOsaka University

Principal Investigator

TAKISAWA Haruhiko  Osaka University, Graduate School of Science, Department of Biological Sciences, Professor, 大学院理学研究科, 教授 (60154944)

Co-Investigator(Kenkyū-buntansha) SHIRAHIGE Katsuhiko  Tokyo Institute of Technology, Gene Research Center, Associate Professor, バイオ研究基盤支援総合センター, 助教授 (90273854)
Project Period (FY) 2001 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥75,200,000 (Direct Cost: ¥75,200,000)
Fiscal Year 2005: ¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 2004: ¥15,600,000 (Direct Cost: ¥15,600,000)
Fiscal Year 2003: ¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2002: ¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2001: ¥14,200,000 (Direct Cost: ¥14,200,000)
KeywordsDNA replication / Initiation complex / GINS / rep liso me / ChIP-chip method / Replication checkpoint / DNA複製因子 / 複製ライセンス化 / 複製チェックポイント / RecQ4 / Sld2 / Tof1 / Tim1 / Csm3 / Tipin / 複製フォーク / Mrc1 / geminin / Dpb11 / Cut5 / TopBP1 / DNA複製制御 / S期CDK / アフリカツメガエル / 無細胞複製系 / MCM / Cdc45 / MCM蛋白質 / DNAヘリカーゼ / Mcmタンパク質
Research Abstract

UsingXenopuseggextracts and budding yeast,we investigatedtheregulationof initiation andelongation stages of DNA replication. We have clarified conserved and diverged regulation mechanisms for DNA replication.
We have identified a novel and highly conserved replication protein complex, GINS, as an essential component required for the assembly of initiation machinery of DNA replication. We have also identified conserved components of replisomes as GINS, Cdc45, Tofl/Timl, Csm3/Tipin and Mrcl/claspin. We have also identified Xenopus homolog of yeast Cut5/Dpb 11 and Sld2/Drc 1 as Xenopus CutS and RecQ4. These proteins show diverged structure and function compared with yeast proteins, suggesting that these proteins gain some additional functions during evolution of metazoans.
We developed a high-density oligonucleotide array that was able to analyze yeast chromosome VI at a 300-base pair (bp) resolution and introduced ChIP-chip (Chromatin immuno-precipitation combined with DNA chip) as a very powerful tool to visualize the dynamic changes of replication proteins and progression of DNA replication. This technology opens up the way to understand how local protein-protein or protein-DNA interactions lead to the dynamic changes of chromosome structure and clarified 1) how DNA replication and cell cycle checkpoint are coordinated, and 2) how DNA transcription is coordinated with sister chromatid cohesion.

Report

(6 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (61 results)

All 2006 2005 2004 2003 Other

All Journal Article (46 results) Book (4 results) Publications (11 results)

  • [Journal Article] Regulation of Replication Licensing by Acetyltransferase Hbol.2006

    • Author(s)
      Iizuka, M.
    • Journal Title

      Mol. Cell. Biol. 26

      Pages: 1098-1108

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Localization of MCM2-7, Cdc45, and GINS to the Site of DNA Unwinding during Eukaryotic DNA2006

    • Author(s)
      Pacek, M.
    • Journal Title

      Mol. Cell 21

      Pages: 581-587

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The N-terminal noncatalytic region of Xenopus RecQ4 is required for chromatin binding of DNA polymerase a in the initiation of DNA replication2006

    • Author(s)
      Matsuno, K.
    • Journal Title

      Mol. Cell. Biol. 26

      Pages: 4843-4852

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The phosphorylated C-terminal domain of Xenopus Cut5 directly mediates ATR-dependent activation of Chk12006

    • Author(s)
      Hashimoto, Y.
    • Journal Title

      Genes Cells 11

      Pages: 993-1007

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protein Phosphatase 2A protects centromeric sister chromatid cohesion.2006

    • Author(s)
      Riedel, C.G.
    • Journal Title

      Nature 441

      Pages: 53-61

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Chromosomal Association of the Smc5/6 Complex Reveals that It Functions in Differently Regulated Pathways.2006

    • Author(s)
      Betts, H.
    • Journal Title

      Mol. Cell 23

      Pages: 755-767

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of Replication Licensing by Acetyltransferase Hbol.2006

    • Author(s)
      Iizuka, M., Matsui, T., Takisawa, H., Smith, M.M.
    • Journal Title

      Mol. Cell. Biol. 26(3)

      Pages: 1098-1108

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Localization of MCM2-7, Cdc45, and GINS to the Site of DNA Unwinding during Eukaryotic DNA.2006

    • Author(s)
      Pacek, M., Tutter, A.V., Kubota, Y., Takisawa, H., Walter, J.C.
    • Journal Title

      Mol. Cell 21(4)

      Pages: 581-587

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The N-terminal noncatalytic region of Xenopus RecQ4 is required for chromatin binding of DNA polymerase a in the initiation of DNA replication.2006

    • Author(s)
      Matsuno, K., Kumano, M., Kubota, Y., Hashimoto, Y., Takisawa, H.
    • Journal Title

      Mol. Cell. Biol. 26(13)

      Pages: 4843-4852

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The phosphorylated C-terminal domain of Xenopus Cut5 directly mediates ATR-dependent activation of Chkl2006

    • Author(s)
      Hashimoto, Y., Tsujimura, T.Sugino, A., Takisawa, H.
    • Journal Title

      Genes Cells 11(9)

      Pages: 993-1007

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protein Phosphatase 2A protects centromeric sister chromatid cohesion.2006

    • Author(s)
      C.G.Riedel, V.L.Katis, Y.Katou, S.Mori, W.Helmhart, M.Galova, M.Petronczki, J.Gregan, B.Cetin, I.Mudrak, E.Ogris, K.Mechtler, L.Pelletier, F.Buchholz, K.Shirahige, K.Nasmyth.
    • Journal Title

      Nature 441(7089)

      Pages: 53-61

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Chromosomal Association of the Smc5/6 Complex Reveals that It Functions in Differently Regulated Pathways.2006

    • Author(s)
      H.Betts Lindroos, L.Strom, T.Itoh, Y.Katou, K.Shirahige*, C.Sjogren
    • Journal Title

      Mol Cell. 22(6)

      Pages: 755-767

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Protein Phosphatase 2A protects centromeric sister chromatid cohesion.2006

    • Author(s)
      C.G.Riedel
    • Journal Title

      Nature (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Screening for candidate genes involved in tolerance to organic solvents in yeast.2006

    • Author(s)
      K.Matsui
    • Journal Title

      Appl Microbiol Biotechnol. (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Loacalization of MCM2-7, Cdc45, and GINS to the Site of DNA Unwinding durine Eukaryotic DNA Replication2006

    • Author(s)
      M.Pacek
    • Journal Title

      Mol.Cell 21・4

      Pages: 581-587

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Regulation of Replication Licensing by Acetyptransferase Hbol2006

    • Author(s)
      M.Iizuka
    • Journal Title

      Mol.Cell.Biol. 26・3

      Pages: 1098-1108

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intrinsic nuclear import activity of geminin is essential to prevent re-initiation of DNA replication in Xenopus eggs.2005

    • Author(s)
      Yoshida, K
    • Journal Title

      Genes Cells 10

      Pages: 63-73

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Glucose-dependent cell size is regulated by a G protein-coupled receptor system in yeast Saccharomyces cerevisiae2005

    • Author(s)
      Takami, H.
    • Journal Title

      Genes Cells 10

      Pages: 193-206

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A checkpoint control linking meiotic S phase and recombination initiation in fission yeast.2005

    • Author(s)
      Tonami, Y.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A 102

      Pages: 5797-5801

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification and characterization of rns4/vps32 mutation in the RNase T1 expression-sensitive strain of Saccharomyces cerevisiae : Evidence for altered ambient response resulting in transportation of the secretory protein to vacuoles.2005

    • Author(s)
      Unno, K.
    • Journal Title

      FEMS Yeast Res 5

      Pages: 801-812

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intrinsic nuclear import activity of geminin is essential to prevent re-initiation of DNA replication in Xenopus eggs.2005

    • Author(s)
      Yoshida, K., Takisawa, H., Kubota, Y.
    • Journal Title

      Genes Cells 10(1)

      Pages: 63-73

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Glucose-dependent cell size is regulated by a G protein-coupled receptor system in yeast Saccharomyces cerevisiae.2005

    • Author(s)
      H.Tamaki, C.W.Yun, T.Mizutani, T.Tsuzuki, Y.Takagi, M.Shinozaki, Y.Kodama, K.Shirahige, H.Kumagai.
    • Journal Title

      Genes Cells 10(3)

      Pages: 193-206

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A checkpoint control linking meiotic S phase and recombination initiation in fission yeast.2005

    • Author(s)
      Y.Tonami, H.Murakami, K.Shirahige, M.Nakanishi.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A. 102(16)

      Pages: 5797-801

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Kitamoto Identification and characterization of ms4/vps32 mutation in the RNase T1 expression-sensitive strain of Saccharomyces cerevisiae : Evidence for altered ambient response resulting in transportation of the secretory protein to vacuoles.2005

    • Author(s)
      K.Unno, P.R.Juvvadi, H.Nakajima, K.Shirahige, K.
    • Journal Title

      FEMS Yeast Res. 5(9)

      Pages: 801-812

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A checkpoint control linking meiotic S phase and recombination initiation in fission yeast.2005

    • Author(s)
      Y.Tonami
    • Journal Title

      Proc.Natl.Acad.Sci.U.S.A. 102・16

      Pages: 5797-5801

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intrinsic nuclear import activity of geminin is essential to preventre-initiation of DNA replication in Xenopus eggs.2005

    • Author(s)
      Yoshida, K.
    • Journal Title

      Genes Cells 10・1

      Pages: 63-73

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Reciprocal association of the budding yeast ATM-related proteins Tell and Mecl with telomeres in vivo2004

    • Author(s)
      Takata, H.
    • Journal Title

      Mol. Cell 14

      Pages: 515-522

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cohesin relocation from sites of chromosomal loading to places of convergent transcriptions.2004

    • Author(s)
      Lengronne, A.
    • Journal Title

      Nature 430

      Pages: 573-578

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Yeast Pho85 kinase is required for proper gene expression during the diauxic shift.2004

    • Author(s)
      Nishizawa, M.
    • Journal Title

      Yeast 21

      Pages: 903-918

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Postreplicative recruitment of Cohesion to double-strand breaks is required for DNA repair.2004

    • Author(s)
      Strom, L.
    • Journal Title

      Mol. Cell 16

      Pages: 1003-1015

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Spo13 Facilitates Monopolin Recruitment to Kinetochores and Regulates Maintenance of Centromeric Cohesion during Yeast Meiosis.2004

    • Author(s)
      Katis, V.L.
    • Journal Title

      Curr. Biol. 14

      Pages: 2183-2196

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Reciprocal association of the budding yeast ATM-related proteins Tell and Mecl with telomeres in vivo.2004

    • Author(s)
      Takata, H.
    • Journal Title

      Mol. Cell 14(4)

      Pages: 515-522

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cohesin relocation from sites of chromosomal loading to places of convergent transcriptions.2004

    • Author(s)
      A.Lengronne, Y.Katou, S.Mori, S.Yokobayashi, G.Kelly, T.Itoh, Y.Watanabe, K.Shirahige*, F.Uhlmann*
    • Journal Title

      Nature 430(6999)

      Pages: 573-578

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Yeast Pho85 kinase is required for proper gene expression during the diauxic shift.2004

    • Author(s)
      M.Nishizawa, Y.Katou, K.Shirahige, A.Toh-E
    • Journal Title

      Yeast 21(11)

      Pages: 903-918

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Sjogren Postreplicative recruitment of Cohesin to double-strand breaks is required for DNA repair.2004

    • Author(s)
      L.Strom, H.B.Lindroos, K.Shirahige, C.
    • Journal Title

      Mol. Cell 16(6)

      Pages: 1003-1015

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Spol3 Facilitates Monopolin Recruitment to Kinetochores and Regulates Maintenance of Centromeric Cohesion during Yeast Meiosis.2004

    • Author(s)
      V.L.Katis, J.Matos, S.Mori, K.Shirahige, W.Zachariae, K.Nasmyth
    • Journal Title

      Curr Biol. 14(24)

      Pages: 2183-2196

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Spo 13 facilitates monopolin recruitment to kinetochores and regulates maintenance of centromeric cohesion during yeast meiosis.2004

    • Author(s)
      Katis, V.L.
    • Journal Title

      Curr.Biol. 14・24

      Pages: 2183-2196

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Postreplicative recruitment of cohesin to double-strand breaks is required for DNA repair.2004

    • Author(s)
      Strom, L.
    • Journal Title

      Mol.Cell 16・6

      Pages: 1003-1015

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cohesin relocation from sites of chromosomal loading to places of convergent transcription.2004

    • Author(s)
      Lengronne, A.
    • Journal Title

      Nature 430

      Pages: 573-578

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Reciprocal association of the budding yeast ATM-related proteins Tell and Mec1 with telomeres in vivo.2004

    • Author(s)
      Takata, H.
    • Journal Title

      Mol.Cell 14・4

      Pages: 515-522

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CDK- and Cdc45-dependent priming of the MCM complex on chromatin during S-phase in Xenopus egg extracts.2003

    • Author(s)
      Masuda, T
    • Journal Title

      Genes Cells 8

      Pages: 145-161

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel ring-like complex of Xenopus proteins essential for the initiation of DNA replication.2003

    • Author(s)
      Kubota, Y.
    • Journal Title

      Genes & Dev. 17

      Pages: 1141-1152

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Xenopus Cut5 is essential a CDK-dependent process in the initiation of DNA replication2003

    • Author(s)
      Hashimoto, Y
    • Journal Title

      EMBO J. 22

      Pages: 2526-2535

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CDK-and Cdc45-dependent priming of the MCM complex on chromatin during S-phase in Xenopus egg extracts.2003

    • Author(s)
      Masuda, T., Mimura, S., Takisawa, H.
    • Journal Title

      Genes Cells 8(2)

      Pages: 145-161

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel ring-like complex of Xenopus proteins essential for the initiation of DNA replication.2003

    • Author(s)
      Kubota' Y., Takase' Y., Komori, Y., Hashimoto, Y., Arata, T., Kamimura, Y., Araki, H., Takisawa, H.
    • Journal Title

      Genes & Dev. 17(9)

      Pages: 1141-1152

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Xenopus Cut5 is essential for a CDK-dependent process in the initiation of DNA replication.2003

    • Author(s)
      Hashimoto, Y., Takisawa, H.
    • Journal Title

      EMBOJ. 22(10)

      Pages: 2526-2535

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Methods in Enzymology "DNA Repair" (edited by J. Campbell)2006

    • Author(s)
      Katou, Y.
    • Total Pages
      575
    • Publisher
      Elsevier Life Sciences (CA)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] DNA複製・修復がわかる(分担 DNA複製のライセンス化)2004

    • Author(s)
      久保田弓子
    • Total Pages
      133
    • Publisher
      羊土社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 細胞核のダイナミックス(分担 再構成核におけるDNA複製の解析)2004

    • Author(s)
      久保田弓子
    • Total Pages
      206
    • Publisher
      シュプリンガー・フェアラーク東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 細胞核のダイナミックス 再構成核におけるDNA複製の解析2004

    • Author(s)
      久保田弓子, 滝澤温彦
    • Total Pages
      12
    • Publisher
      シュプリンガー・フェアラーク東京
    • Related Report
      2004 Annual Research Report
  • [Publications] Masuda, T., Mimura, S., Takisawa, H.: "CDK- and Cdc45-dependent priming of the MCM complex on chromatin during S-phase in Xenopus egg extracts."Genes Cells. 8. 145-161 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kubota, Y., Takase, Y., Komori, Y., Hashimoto, Y., Arata, T., Kamimura, Y., Araki, H., Takisawa, H.: "A novel ring-like complex of Xenopus proteins essential for the initiation of DNA replication."Genes & Dev.. 17・3. 1141-1152 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hashimoto, Y., Takisawa, H.: "Xenopus Cut5 is essential for a CDK-dependent process in the initiation of DNA replication."EMBO J.. 22・10. 2526-2535 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kubota, Y., Takisawa, H.: "Block to DNA replication in meiotic maturation : a unified view for a robust arrest of cell cycle in oocytes and somatic cells."BioEssays. 25・4. 313-316 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 久保田弓子, 吉田真和, 滝澤温彦: "DNA複製・修復がわかる 基本編2章 DNA複製のライセンス化"羊土社. 9 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masuda, T.: "CDK-and Cdc45-dependent priming of the MCM complex on chromatin during S-phase in Xenopus egg extracts"Genes Cells. 8. 145-161 (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 Dev.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Kubota, Y.: "Block to DNA replication in meiotic maturation"BioEssays. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] 滝澤温彦: "ゲノムの複製と分配 分担執筆 複製開始複合体の形成 真核生物"シュプリンガー・フェアラーク東京. 60-67 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Waga, S.: "DNA polymerase e is required for coordinated and efficient chromosomal DNA replication in Xenopus egg extracts"Proc.Natl.Acad.Sci.USA. 98・9. 4978-4983 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Gotoh, T.: "nactivation of the checkpoint kinase Cds1 is dependent on cyclin B-Cdc2 kinase activation at the meiotic G2/M-phase transition in Xenopus oocytes"J.Cell Sci.. 114・18. 3397-3406 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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