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Regulation of eukaryotic DNA replication by phosphotidylinosities.

Research Project

Project/Area Number 02454155
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionNagoya University

Principal Investigator

YOSHIDA Shonen  Nagoya University School of Medicine, Institute for Disease Mechanism and Control, Associate Professor., 医学部, 助教授 (70090420)

Co-Investigator(Kenkyū-buntansha) KOJIMA Kiyohide  Nagoya Univ. Sch. Med. Professor, 医学部, 教授 (80073104)
IZUTA Shunji  Nagoya Univ. Sch. Med. Research Associate, 医学部, 助手 (50203047)
KOIZUMI Keiko  Nagoya Univ. Sch. Med. Assistant Professor, 医学部, 講師 (00118027)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥5,400,000 (Direct Cost: ¥5,400,000)
KeywordsDNA polymerase alpha / DNA replication / Phospholipase C / PIP / IP2 / Regenerating Liver / Nuclei / Phosphotidylinositides / PlP / lP_2 / カルジオリピン / P1P / 1P_2 / ホスフォリパ-ゼC
Research Abstract

Previously, we showed that DNA polymerase alpha, beta, and gamma were strongly supressed by PI, which bound to hydrophobic region (DNA binking domain) of the enzyme molecules (Yoshida et al. 1988). It was also shown that PI and cardiolipin strongly inhibited the in vitro replication of human c-myc ARS. This inhibition is due, at least in part, to the inhibition of topoiso merase I (Umekawa et al.). It was reported that PIP or IP2 activated DNA polymerase alpha (Syl via et al.). These results suggest that DNA replication is regulated by PI and its metabolites. In this context, we tested the effects of phosphoinositides or their derivatives and found that a crude fraction of DNA polymerase alpha (low specific activity form) was stimulated by IP2. However, After purification of the fraction by Mono Q column chromatography (FPLC, Phrmiacia), the stimulation disappeared, and was restored by the addition of flow-through fraction. These results indicate that IP2 stimulate enzyme indirectly, via an modifing factor of DNA polymerase alpha. We are now purifing this protein factor. On the other hand, we also found that cell nuclei contained a considerable amount of phospholipase C (PL C) which is specific for phosphoinositides. The nuclear PLC was purified and separated into four distinct molecular species. One of them, 88 kDa nPLC, was found to be specific to nuclei of growing cells, such as regenerating liver or ascites hepatoma, but absent in resting liver cell. This activity increased transiently at S-phase of liver regeneration.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Iwata,M.: "Sequence-dependent termination of mammlian DNA polymerase reaction by a new platinum compound(-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)platinum(II)monohydrate." Jpn.J.Cancer Res.82. 433-498 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Izuta,S.: "The 5'-triphosphate of 3'-azido-3'-deoxythymidine and 2',3'-dideoxynucleosides inhibit DNA polymerase γ by different mechanisms." Biochem.Biophys.Res.Commun.179. 776-783 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shioda,M.: "Stimulation of DNA polymerase α activity by microtubule-associated proteins." Biochemistry. 30. 11403-11412 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroshi Kuriki: "Existence of phosphoinositide-specific phospholipase C in rat liver nuclei and its change during liver regeneration" J.Biochem.111. 283-286 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroo Ishihara: "Growth-associated changes in fatty acid compositions of nuclear phospholipids of liver cells." Biocim.Biopys.Acta. 1084. 53-59 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Masahiko Asano: "Purification and characterization of four forms of phosphoinositide-specific phospholipase C.from nuclei of rat ascites hepatoma cells."

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Terasaki,M.: "Induction of DNA replication and cell ggowth in rat liver by obstructive jauncive." Jpn.J.Cancer Res.82. 170-175 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Izuta,S.: "Mechanism of Inhibition of DNA polymerase by nucleotide analogues having anti-HIV activities." Nucleic Acids Res.Symp.Series. 25. 79-80 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Murate,T.: "Aphidicolin,an inhibitor of DNA replication,blocks the TPA-induced differentiation of a human megakaryoblastic cell line,MEG-O1." Blood. 78,. 3168-3177 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Iyomasa,S.: "Decrease in regeneration capacity of rat liver after external biliary drainage." Eur.Surg.Res.(1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Murakami-Murofushi,K.: "Isolation of a novel lysophosphatidic acid which inhibits eukaryotic DNA polymerase a from myxoamoebae of physarum polycephalum." J.Biol,Chem.(1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Terasaki, M., Kuriki, H., Nimura, Y., Shionoya, S., Kojima, K. and yoshida, S.: "Induction of DNA replication and cell growth in rat liver by obstructive jaundice." Jpn. J. Cancer Res.82. 170-175 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ishihara, H., T-koizumi, K., Kuriki, H., Yoshida, S. and Kojima, K.: "Growth-associated changes in fatty acid compositions of nuclear phospolipids of liver cells." Biochim. Biophys. Acta. 1084. 53-59 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Iwata, M., Izuta, S., Suzuki M., Kojima, K., Furuhashi, Y., Tomoda, Y. and Yoshida, S.: "Sequence-dependent termination of mammalian DNA polymerase reaction by a new platinum compound (-) - (R) -2-aminomethylpyrrolidine (1, 1-cyclobutane-Dicarboxylato) -2-phatinum (II) monohydrate" Jpn. J. Cancer Res.82. 433-439 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Izuta, S., Saneyoshi, S., Sakurai, T., Suzuki, M., Kojima, K. and Yoshida, S.: "The 5'-triphosphates of 3'-deoxythymidine and 2', 3'-azido-3'-dideoxynucleosides inhibit DNA polymerase gamma by different mechanisms." Biochem. Biophys. Res. Commun.179. 776-783 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shioda, M., Okuhara, K., Murofushi, H., Mori, A., Sakai, H., Murakami-Murofushi, K., Suzuki, M. and Yoshida, S.: "Stimulation of DNA polymerase alpha activity by microtubule-associated protein." Biochemistry. 30. 11403-11412 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Izuta, S., Saneyoshi, S., Sakurai, T., Suzuki, M., Kojima, K. and Yoshida, S.: "Mechanisms of inhibitions of DNA polymerase gamma by nucleotide analogues having anti-HIV activities." Nucleic Acids Res. Symp. Serles. 25. 79-80 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Murate, T., Hotta, T., Tsushita, K., Suzuki, M., Yoshida, M., Saito. H. and Yoshida, S.: "Aphidicolin, an inhibitor of DNA replication, Blocks the TPA-induced differentiation of a human megakaryoblastic cell line, MEG-01." Blood. 78. 3168-3177 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kuriki, H., T-Koizumi, K., Asano, M., Yoshida, S., Kojima, K. and Nimura, Y.: "Existence of phosphoinostitide-specific phospholipase C in rat liver nuclei and its change during liver regeneration." J. Biochem. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Iyomasa, S., Terasaki, M., Kuriki, H., nimura, Y., Shionoya, S., Kojima, K. and Yoshida, S.: "Decrease in regeneration capacity of rat liver after external biliary drainage." Eur. Surg. Res.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Murakami-Murofushi, K., Shioda, M., Kaji, K., Yoshida, S. and Murofushi, H.: "Isolation of a novel lysophosphatidic acid which inhibits eukaryotic DNA polymerase alpha from myxoamoebae of physarum polycephalum." J. Biol. Chem.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Asano, M., Koizumi, K., Kojima, K., and Yoshida, S.: "Purification and characterization of four forms of phosphoinositide-specific phospholipase C from nuclei of rat ascites hepatoma cells." J. Biol. Chem.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Iwata,M.: "Sequenceーdependent termination of mammlian DNA polymerase reaction by a new platinum compound(-)ー(R)ー2ーaminomethylpyrrolidine(1,1ーcyclobutaneーdicarboxylato)platinum(II) monohydrate." Jpn.J.Cancer Res.82. 433-498 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Izuta,S.: "The 5'ーtriphosphate of 3'ーazidoー3'ーdeoxythymidine and 2',3'ーdideoxynucleosides inhibit DNA polymerase γ by different mechanisms." Biochem.Biophys.Res.Commun.179. 776-783 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shioda,M.: "Stimulation of DNA polymerase α activity by microtubuleーassociated proteins." Biochemistry. 30. 11403-11412 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hiroshi Kuriki: "Existence of phosphoinositideーspecific phospholipase C in rat liver nuclei and its change during liver regeneration" J.Biochem.111. 283-286 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hiroo Ishihara: "Growthーassociated changes in fatty acid compositions of nuclear phospholipids of liver cells." Biocim.Biopys.Acta. 1084. 53-59 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Masahiko Asano: "Purification and characterization of four forms of phosphoinositideーspecific phospholipase C.from nuclei of rat ascites hepatoma cells."

    • Related Report
      1991 Annual Research Report
  • [Publications] Terasaki,M.: "Induction of DNA replication and cell ggowth in rat liver by obstructive jauncice." Jpn.J.Cancer Res.82. 170-175 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Izuta,S.: "Mechanism of Inhibition of DNA polymerase by nucleotide analogues having antiーHIV activities." Nucleic Acids Res.Symp.Series. 25. 79-80 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Murate,T.: "Aphidicolin,an inhibitor of DNA replication,blocks the TPAーinduced differentiation of a human megakaryoblastic cell line,MEGー01." Blood. 78,. 3168-3177 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Iyomasa,S.: "Decrease in regeneration capacity of rat liver after external biliary drainage." Eur.Surg.Res.(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] MurakamiーMurofushi,K.: "Isolation of a novel lysophosphatidic acid which inhibits eukaryotic DNA polymerase α from myxoamoebae of physarum polycephalum." J.Biol.Chem.(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Murate,T.: "Terminal diferentiation of human erythroleukemia cell line K562 induced by aphidicolin." Experimental Cell Research. 191. 45-50 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Terasaki,M.: "Induction of DNA replication and cell growth in rat liver by obstructive jaundice." Japanese Journal of Cancer Research. 81. 170-175 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Murate,T.: "Characterzation of araーC induced commitment of K562 cells and essential role of new protein synthesis during commitment process."

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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