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

Complementation assisted positional cloning of the gene for AT variant.

Research Project

Project/Area Number 10672136
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human genetics
Research InstitutionHiroshima University

Principal Investigator

MATSUURA Shinya  Research Institute for Radiation Biology and Medicine, Hiroshima University, Associate Professor, 原爆放射能医学研究所, 助教授 (90274133)

Co-Investigator(Kenkyū-buntansha) TAUCHI Hiroshi  Research Institute for Radiation Biology and Medicine, Hiroshima University, Research Associate, 原爆放射能医学研究所, 助手 (70216597)
KOMATSU Kenshi  Research Institute for Radiation Biology and Medicine, Hiroshima University, Professor, 原爆放射能医学研究所, 教授 (80124577)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsNijmegen syndrome / Cancer prone disorder / Ataxia-telangiectasia / Radiosensitivity / Positional cloning / NBS1 / Xrs2 / Nijmegen breakage症候群 / Ataxia-telangiectasia / 染色体不安定症候群 / NBSI / 8q21 / DNA修復 / テロメア / 減数分裂
Research Abstract

Nijmegen syndrome is an autosomal recessive disorder characterized by microcephaly, growth retardation, severe combined immunodeficiency, and a high incidence of lymphoid cancers. Cells from NBS patients display chromosome instability, hypersensitivity to ionizing radiation, and an abnormal cell cycle regulation after irradiation. We mapped the. NBS gene at 8q21-24 by functional complementation assays using microcell-mediated chromosome transfer. Only a fragment of chromosome 8q complemented the sensitivity to ionizing radiation in NBS cell lines. We then succeeded in YAC complementation in the NBS cell, and substantially narrowed the NBS critical region to an 800 kb interval. Finally, we identified the NBS1 gene, which is mutated in NBS patients. The 5-bp-deletion, 657-661delACAAA, was found to be founder mutation. The gene is 50 kb long and encodes a protein of 754 amino acids. A weak homology in the N-terminal region was identified with the yeast Xrs2 proteins. Expression of the 2.6 kb transcripts is enhanced in the testis. These results suggested that the NBSM gene might be involved in meiotic recombination.

Report

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

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Ito,A.,et al.: "Expression of full-length NBSI protein restores normal radiation responses in cells from Nijmegen breakage syndrome patients"Biochem.Biophys.Res.Commun.. 265. 716-721 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tauch,H.,et al.: "Seguence analysis on 800kb genomic DNA region on chromosome 8g21,which contains theNijmagen breakage syndrome gane,NBSI"Genomics. 55. 242-247 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiramoto,T.,et al.: "Mutation of a novel RAD54 homologue,RAD54B,in primary cancer"Oncogene.. 18. 3422-3426 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura,A.,et al.: "Four novel mutations of the Fanconi anemid group A gene(FAA)in Japanese patients"J.Hum.Genet.. 44. 48-51 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuura,S.,et al.: "Positional cloning of the gene for Nijmegen breakage syndrome"Nature Genet.. 19. 179-181 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuura,K.,et al.: "Radiation induction of p53 in cells from Nijmegen breakage syndrome is defective but not similar to ataxia-telangiectasia"Biochem.Biophys.Res.Commun.. 242. 602-607 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito A., Tauchi, H., Kobayashi, J., Morishima, K., Nakamura, A., Hirokawa, Y., Matsuura, S., Ito, K., Komatsu, K.: "Expression of full-length NBS1 protein restores normal radiation responses in cells from Nijimegen breakage syndrome patients."Biochem. Biophys. Res. Commun.. 265. 716-721 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tauchi, H., Matsuura, S., Isomura, M., Kinjo, T., Nakamura, A., Sakamoto, S., Kondo, N., Endo, S., Komatsu. K., and Nakamura Y.: "Sequence analysis of an 800-kb genomic DNA region on chromosome 8q21, which contains the Nijmegen breakage syndrome gene, NBS1."Genomics. 55. 242-247 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiramoto, T., Nakanishi, T., Sumiyoshi, T., Fukuda, T., Matsuura, S., Tauchi, H., Komatsu, K., Shibasaki, M., Sumii, M., Kajiyama, G., Kamada, N., Miyagawa, K., and Kamiya, K.: "Mutations of a novel human RAD54 homologue, RAD54B, in primary cancer."Oncogene. 18. 3422-3426 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura, A., Matsuura, S., Tauchi, H., Hanada, R., Ohashi, H., Hasegawa, T., Honda, K., Masuno, M., Imaizumi, K., Sugita, K., Ide, T., and Komatsu, K.: "Four novel mutations of the Fanconi anemia group A gene (FAA) in Japanese patients."J. Hum. Genet.. 44. 48-51 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuura, S., Tauchi, H., Nakamura, A., Kondo, N. Sakamoto, S., Endo, S., Smeets. D., Solder, B., Belohradsky, B. H., Kaloustian, V., M., Oshimura, MA Isomura. M., Nakamura, Y., and Komatsu, K.: "Positional cloning of the gene for Nijmegen breakage syndrome."Nature Genet. 19. 179-181 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuura, K., Balmukhanov, T., Tauchi, H., Weemaes. C., Smeets. D., Chrzanowska, K., Endo, S., Matsuura, S., and Komatsu, K.: "Radiation induction of p53 in cells from Nijmegen breakage syndrome is defective but not similar to ataxia-telangiectasia."Biochem. Biophys. Res. Commun.. 242. 602-607 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito,A.,et al.: "Expression of full-length NBSI protein restores normal radiation responses in cells form Nijmegen breakage syndrome patients."Biochem. Biophys. Res. Commun.. 265. 716-721 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morishima,K.,et al.: "A polymophic CA repeat marker at the human 27-KD calbirdin (CALBI) locus"J. Hum. Genet.. 44. 415-416 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tauchi,H.,et al.: "Sequence analysis of an 800Kb genomic DNA region on chromosome 8g21,Which contains the Nijmegen breakage syndrome gene,NBSI"Genomics. 65. 242-247 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiramoto,T.,et al.: "Mutations of a novel human RAD54 homologue,RAD54B,in primary cancer"Oncogene. 18. 3422-3426 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakamura,A.,et al.: "Four novel mutations of the Fanconi anemia group A gene (FAA) in Japanese patients"J. Hum. Genet.. 44. 48-51 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Tauchi, et.al.: "Sequence analysis of an 800-kb genomic DNA region on chromosome 8q21 that contains the Nijmegen breakage syndrome gene, NBSI" Genomics. 55. 242-247 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Hiramoto, et.al.: "Mutations of novel human RAD54 homologue, RAD54B, in primary cancer" Oncogene. 印刷中. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] A.Nakamura, et.al.: "Four novel mutations of Fanconi anemia group A gene (FAA) in Japanese patients" J.Hum.Genet.44. 48-51 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Matsuura, et.al.: "Positional cloning of the gene for Nijmegen breakage syndrome" Nature Genet.19. 179-181 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Matsuura, et.al.: "Radiation induction of p53 in cells form Nijmegen breakage syndrome is defective but not similar to ataxia-telangiectasia" Biochem.Biophys.Res.Commun.242. 602-607 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Komatsu, et.al.: "Radiation induction of p53 in cells from Nijmegen breakage syndrome and functional mapping of the underlying gene at 8q21" Disease Markers. 14. 26-27 (1998)

    • Related Report
      1998 Annual Research Report

URL: 

Published: 1998-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi