1999 Fiscal Year Final Research Report Summary
Complementation assisted positional cloning of the gene for AT variant.
| Project/Area Number |
10672136
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human genetics
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| Research Institution | Hiroshima University |
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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)
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| 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)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Nijmegen syndrome / Cancer prone disorder / Ataxia-telangiectasia / Radiosensitivity / Positional cloning / NBS1 / Xrs2 |
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| 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.
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[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)
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「研究成果報告書概要(欧文)」より
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[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
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
