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Cloning of an immortality-suppressor gene on human chromosome 7

Research Project

Project/Area Number 09044234
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionKihara Institute for Biological Research

Principal Investigator

AYUSAWA Dai  Kihara Institute for Biological Research Professor, 木原生物研究所, 教授 (00142109)

Co-Investigator(Kenkyū-buntansha) SUZUKI Toshikazu  Kihara Institute for Biological Research Assistant Professor, 木原生物研究所, 助手 (70270527)
FUJII Michihiko  Kihara Institute for Biological Research Assistant Professor, 木原生物研究所, 助手 (80285155)
SCHERER Step  トロント小児病院, 遺伝部, 研究員
TUSI Lap Che  トロント大学, 医学部, 教授
SCHERER Ste  トロント小児病院, 遺伝部, 研究員
TSUI Lap Che  トロント大学, 医学部, 教授
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordschromosome 7 / microcell-mediated chromosome transfer / YAC / BAC / radiation hybrid / senescence / telomerase / telomere / STS marker / 細胞不死化 / 遺伝子
Research Abstract

Approximately 50% of immortal human cell lines so far tested seem to have a mutation on a gene on human chromosome 7 since introduction of this chromosome by microcell-mediated chromosome transfer specifically suppress their division potential. To identify it, we prepared a panel of radiation hybrids which contain a small segment of human chromosome 7 under mouse cell background. By chromosome transfer and PCR with STS markers, we narrowed down the gene within a 2-3 Mb region of the chromosome. We planned to rescue human DNA form the hybrids with a newly developed TAR (Transformation Associated Recombination) cloning system in yeast. In collaboration with NIH that invented the cloning system, we prepared a YAC/BAC library from one radiation hybrid. These BAC clones were introduced to human Met5A cell line to examine their anti-proliferative activity against this cell line.
As by-products of this study, we have shown that the immortality suppresser gene negatively regulates the telomere maintenance mechanisms in particular human cell lines. Upon introduction of the gene into the telomerase-positive lines, the telomerase catalytic subunit gene was down-regulated before entering senescence and with shortening of telomeres. In the negative lines, their usually long telomeres were immediately shortened.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Michishita, E., et al: "Brmodeoxyundine induces semesce***-like phenomena in **** cells re**** * *types or species"J. Biochem.. 126. 1052-1059 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakabayashi, K., et al.: "Introduction of chromo some 7 suppresses telum***se with shortoning of telomeres in a human m**thelial cell line"Exp. Cell Res.. 252. 376-382 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suzuki, t., et al.: "Enhanced expression of glniose tr*sp**er GLUT3 in ***** Hola cell ****"Eur., J. Biochem.. 262. 534-540 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujii, M., et al.: "Dephosphorylstion specific p**teins during induction at senescence in immaortal human ***** expressing therm*** SV40T antigen"Biosci, Biotechnol,Biochem.. 63. 1116-1118 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujii, M., et al: "The introduction of **** **** p53 mutomts suppresses **** ****-**** sonescence in immortal human firroblosts"J. Biochem. 125. 531-536 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujii, M., Joguchi, A., Ogino, H., Nakabayashi, K., and Ayusawa, D.: "Dephosphorylation of specific proteins during induction of senescence in immortal human fibroblasts expressing thermlabile SV40 T antigen.Biosci."Biotechnol. Biochem.. 63. 1116-1118 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujii, M., Ide, A., Nakabayashi, K., Joguchi, A., Ogino, H., and Ayusawa, D.: "The introduction of dominant-negative p53 mutants suppresses temperature shift-induced senescence in immortal human fibroblasts expressing a thermolabile SV40 large T antigen."J. Biochem.. 125. 531-536 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakabayashi, K., Ogino H., Michishita, E., Satoh, N., and Ayusawa, D.: "Introduction of chromosome 7 suppresses telomerase with shortening of telomeres in a human mesothelial cell line."Exp. Cell Res.. 252. 376-82 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Michishita, E., Nakabayashi, K., Suzuki, T., Kaul, S. C., Ogino, H., Fujii, M., Mitsui, Y., and Ayusawa, D.: "5-Bromodeoxyuridine Induces Senescence-like Phenomena in Mammalian Cells Regardless of Cell Types or Species"J. Biochem.. 126. 1052-14059 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Michishita,E.,et al.: "Brumodeoxyueidine induces senescence-like phenomena in mammalion cells regardlesc of cell tyes or species"J.Biochem.. 126. 1052-1059 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakabayashi,K.,et al.: "Introduction of chromo some 7 suppresses telomerase with shortening of telomeres in a luman mesothelial cell line."Exp.Cell Res.. 252. 376-382 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki,T.,et al.: "Enhanced expression of glncose transporter GLUT3 in tumorigenic Hola cell hylorids."Eur.J.Biochem.. 262. 534-540 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujii,M.,et al.: "Dephosphorylation specific proteins during induction of senescence in immortal human fihroblcsts expressing the mlabile SV40T antigln"Biosci,Biotechnol,Biodrem,. 63. 1116-1118 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujii,M.,et al.: "The introduction of daminant-negative p53 mutants suppresses tenperature chift-inclucecl sonescence in immortal human fibroblasts …"J.Biochem,. 125. 531-536 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 鮎沢 大: "DNA topoisomerase inhibitors induce reversible senescence in normal human fibroblasts" Biochem Biophys Res Commun. 258. 667-671 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 鮎沢 大: "Clustering of human chromosome fragments on the mouse genome by chromosome-mediated gene transfer" DNA Res. 5. 247-250 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 鮎沢 大: "Suppression of senescence in normal human fibroblasts by introductionof dominant-negative p53 mutants or human papilloma virus type 16 E6 protein" Biosci Biotechnol Biochem.62. 1458-1460 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 藤井道彦: "A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes" Nature. 394. 694-697 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 鮎沢 大: "Release of telomeric DNA from chromosomes in immortal human cells lacking telomerase activity" Biochem Biophys Res Commun. 248. 223-227 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 鮎沢 大: "細胞老化/不死化研究の現状" BIO INDUSTRY. 15. 5-30 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 鮎沢 大: "Decrease in amplified telomeric and sequences induction of senescence markers by introduction of human chromosome 7 or its segments in SUSM-1" Ekp.Cell Res.235. 345-353 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 藤井 道彦: "A novel superoxide dismutase gene encoding a membrane-bound and an extracellular isoforms by alternative splicing in C. elegans" DNA Res.(印刷中). (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 鮎沢 大: "D群細胞の不死化抑制遺伝子" 最新医学. 52. 348-353 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 鮎沢 大: "ヒト細胞老化にかかわる遺伝子" 実験医学. 15. 214-219 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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