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

Regulatory mechanisum for maintainance of genetic information

Research Project

Project/Area Number 05270102
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionKyoto University

Principal Investigator

UTSUMI Hiroshi  Research Reactor Institute, Kyoto University, Radiation Life Science, Professor, 原子炉実験所, 教授 (20025646)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Kazuo  Graduate School of Science, Tohoku University, Professor, 大学院・理学研究科, 教授 (20093536)
NIKAIDO Osamu  Faculty of Pharmaceutical Science, Kanazawa University, Division of Radiation Bi, 薬学部, 教授 (60019669)
MATSUKAGE Akio  Laboratory of Cell Biology, Aichi Cancer Research Institute, Chief, 生物学部, 部長 (90019571)
KASAI Hiroshi  Institute of Industrial Ecology Sciences, University of Occupational and Environ, 産業生態科学研究所, 教授 (40152615)
ISHIZAKI Kanji  Laboratory of Experimental Radiology, Aichi Cancer Research Institute, Chief, 放射線部, 部長 (70111987)
宮越 順二  京都大学, 医学部, 講師 (70121572)
八木 孝司  京都大学, 医学部, 助教授 (80182301)
松永 司  金沢大学, 薬学部, 助手 (60192340)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥116,800,000 (Direct Cost: ¥116,800,000)
Fiscal Year 1995: ¥40,000,000 (Direct Cost: ¥40,000,000)
Fiscal Year 1994: ¥41,800,000 (Direct Cost: ¥41,800,000)
Fiscal Year 1993: ¥35,000,000 (Direct Cost: ¥35,000,000)
Keywordscaffeine / 8-hydroxyguanine / (6-4) photoproduct / DNA polymerase alpha / PCNA / p53-deficient / hMSH3 / 8-ヒドロキシグアニン(oh8Gua) / p53欠損細胞 / PCNA / PCNAとXPAタンパク質との相互作用 / 8-ヒドロキシングアニン(oh8Gua) / interstrand cross-links / PCNAとXPACタンパク質との相互作用 / 8-ヒドロキシグアニン(oh^8Gua) / XPE-BF
Research Abstract

Utsumi found that factors induced the potentially lethal damage recovery exist in the conditioned medium and are smaller than MW 1000. He also isolated a radiation-sensitive mutant of V79 Chinese hamster cells, which become radio-resistant in presence of caffeine after X-ray irradiation. He showed that this caffeine induced resistance is specific to cell killing by the interstrand cross-link damages. Ihsizaki revealed that much more number of sister chromatid exchanges and less growth arrest were induced by UV in p53-deficient mouse cells than in p53-proficient cells a though p53-deficient cells were no more sensitive to UV or X-ray than normal cells. Kasai found that repair activity for 8-hydroxyguanine, one of the major oxidative DNA damages, is enhanced by cellular oxidative stress. He also found other types of oxidative DNA damage, 2-hydroxyadenine and glyoxal formations, which suggested new mechanisms of mutations. 2-Hydroxyadenine and appeared to induce AT*GC and CG*TA mutations … More by base-pairing with T or C.Matsukage has identified a common regulatory element DRE (DNA replication-related element) and a specific transcription factor DREF (DRE-binding factor) which regulate the transcription of a number of Drosophila DNA replication factors such as DNA polymerase alpha and PCNA.The DREF cDNA and gene have been cloned. Furthermore, he found that the ectopic expression of DREF in the eye imaginal disc of transgenice flies repressed differentiation and induce unusual DNA replication. indicating the central role of DREF in cell growth regulation. Nikaido have purified a UV-damaged DNA-binding protein from HeLa cells to homogeneity. They found that it was identical to glyceraldehyde-3-phosphate dehydrogenase, based on the partial amino acid sequence analysis as well as immunological and biochemical analyzes. Miyakoshi reported that human osteosarcoma cells, which have a deletion in p53 gene, become sensitive to ionizing radiation after introduction of wild-type p53. Yamamoto demonstrated that active oxygen species induced (an) as yet identified lesion (s) which leaded to GC*CG tran sversion. Mitani found that (6-4) photolyase could be induced by UVA,blue light, hydrogen peroxide, and growth inhibition by transcriptional regulation or post-transcriptional regulation like photolyase for cyclobutane pyrimidine dimers. Kohno showed that the Dxpa protein was strongly expressed in the central nervous system and muscles as revealed by immunohistochemical analysis using anti-Dxpa antibodies. Ikejima found that expression of the hMSH3 gene, one of the human MutS homologues, significantly decresed in some patients with hematological malignancies and suggested that inactivation of the hMSH3 gene may be involved in leukemogenesis. Genomic structure of the hMSH3 gene was elucidated and it became possible to study the involvement of specific mutations of the gene in some diseases. Fujiwara characterized the group D of Xeroderma pigmentosum. Uchida isolated Droso Less

Report

(4 results)
  • 1996 Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • 1993 Annual Research Report

Research Products

(36 results)

All Other

All Publications

  • [Publications] Utsumi,H.: "Cellular effect of thermal neutron capture treatment using ^<10>B_1-para-boronophenyl-alanine:Lethal effect on melanoma cells with different degrees of X-ray sensitivity." J.Radiation Research. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Utsumi,H.: "Inhibitors of poly(ADP-ribose)synthesis inhibit the two types of repair of potentially lethal damage." Int.J.Radiation Oncology Biol.Phys.29. 577-578 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ishizaki,K.: "UV-induced mutations of supF gene on a shuttle vector plasmid in p53-deficient mouse cells are qualitatively different from those in wild-type cells." Mutat.Res.364. 43-49 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kamiya,H.: "Effects of sequence contexts on misincorporation of nucleotides opposite 2-hydroxyadenine." FEBS Lett.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takahashi,Y.: "DNA replication-related elements cooperate to enhance promoter activity of the drosophila DNA polymerase α 73-kDa subunit Gene." J.B.C.271. 14541-14547 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Wakasugi,M.: "Purificationa of a novel UV-damaged-DNA binding protein highly specific for(6-4)photoproducts." Nucl.Acid.Res.24. 1099-1104 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Utsumi, H.: "Cellular effect of thermal neutron capture treatment using ^<10>B_1-para-boronophenyl-alanine : Lethal effect on melanoma cells with different degrees of X-ray sensitivity." J.Radiation Research. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Utsumi, H.: "Inhibitors of poly (ADP-ribose) synthesis inhibit the two types of repair of potentially lethal damage." Int.J.Radiation Oncology Biol.Phys.29. 577-578 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ishizaki, K.: "UV-induced mutations of supF gene on a shuttle vector plasmid in p53-deficient mouse cells are qualitatively different from those in wild-type cells." Mutat.Res.364. 43-49 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kamiya, H.: "Effects of sequence contexts on misincorporation of nucleotides opposite 2-hydroxyadenine." FEBS Lett.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takahashi, Y.: "DNA replication-related elements cooperate to enhance promoter activity of the drosophila DNA polymerase alpha 73-kDa subunit Gene." J.B.C.271. 14541-14547 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Wakasugi, M.: "Purificationa of a novel UV-damaged-DNA binding protein highly specific for (6-4) photoproducts." Nucl.Acid.Res.24. 1099-1104 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka,H.,et al.: "Characterization of P53 gene mutations in esophageal squamous cerll carcinoma cell lines:Increased frequency and different spectrum of mutations from primary tumors." International Journal of Cancer. 63. 372-376 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kato,M.V.,et al.: "Delayed develpment of retinoblastoma asociated with loss of a maternal allele on chromosome 13." International Journal of Cancer. 64. 3-8 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Akasaka,S.and Yamamoto,K.: "Mutational specificity of the ferrous ion in a supF gene of Escherichia coli." Biochemical and Biophysical Research Commucications. 213. 74-80 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Miyakoshi,J.et al: "Changes in radiation sensitivity of human osteosarcoma cells after p53 introduction" Japanese Journal of Cancer Research. 86. 711-713 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kamiya,H.and Kasai,H.: "Formation of 2-ydroxyadenosine triphosphate,an oxidatively damaged nucleotide,and its incorporation by DNA polymerases." The Journal of Biological Chemistry. 270. 19446-19450 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsukage,A.,et al.: "The DRE sequence TATCGTA,a putative promoter-activating element for Drosphila melanogaster cell-proliferation-related genes." Gene. 166. 233-236 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Utsumi,H.,Elkind,M.M.,: "Inhibitors of poly(ADP-ribose)synthesis inhibit the two types of repair of potentially lethal damage." Int.J.Radiation Oncology Biol.Phys.29. 577-578 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Homma,Y.,Tsunoda,M.,Ksai,H.: "Evidence for the accumulation of oxidative stress during cellular ageing of human diploid fibroblasts." Biochem.Biophys.Res.Commun.,. 203. 1063-1068 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Akasaka,S.,Yamamoto,K.,: "Hydrogen peroxide induces G:C to T:A and G:C to C:G transversion in the supF gene of Escherichia coli." Mol.Gen.Genet.243. 500-505 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ishizaki,K.,et al.,: "Increased UV-induced SCE but normal repair of DNA damage in p53-deficient mouse cells." Int.J.Cancer. 58. 254-257 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Miyakoshi,J.,et al.: "A new designed experimental system for exposure of mammalian cells toextremely low frequency magnetic fields." J.Raidat.Res.35. 26-34 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Matsuoka,S.,Yamaguchi,M.,Matukage,A.: "D-tyep cyclin binding regions of proliferating cell nuclear antigen." J.Biol.Chem.269. 11030-11036 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Utsumi,H.,et al.: "Human melanoma cells:the relationship between their radiosensitivity and the repair of potentially lethal damage." Radiat.Oncol.Invest.,. 1. 29-33 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Habuchi,T.,et al.: "Influence of cigarette smoking and schistosomiasis on p53 gene mutation in urothelial cancer." Cancer Res.,. 53. 3795-3799 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakai,H.,et al.: "p53 Gene mutations and loss of a chromosome 17p in Philadelphia chromosome(Ph1)-positive acute leukemia." Leukemia. 7. 1547-1551 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yamamoto,et al.: "Elevated level of 8-hydroxyguanosine residue in DNA of liver,kidney and brain of Long-Evans Cinnamon rats." Jap.J.Cancer Res.,. 84. 508-511 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kasai,H.,et al.: "Formation of 8-hydroxyguanine by oxidative DNA damage,its repair and its mutagenic effects." Adv.Mutagenesis Res.,. 4. 31-45 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Bessho,t.,et al.: "Repair of 8-hydroxyguanine in DNA by mammalian N-methylpurine-DNA glycosylase." Proc.Natl.Acad.Sci.,. 90. 8901-8904 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Leey.S.,et al.: "Identification of 8-hydroxyguanine glycosylase activity in mammalian tissues using 8-hydrosyguanine specific monoclonal antibody." Biochim.Biophys.Res.Commun.,. in press.

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsunaga,T.,et al.: "Establishment and characterization of a monoclonal antibody recognizing the Dewar isomers of(6-4)photoproducts." Photochem.Photobiol.,. 57. 934-940 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Numata,et al.: "Identification of cellular defect in UVS1,a UV-sensitive Chinese hamster ovary mutant cell line." Cancer Res.,. 53. 495-499 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sato,M.,et al.: "Ultraviolet-specific mutations in p53 gene in skin tumors in xeroderma pigmentosum patients." Cancer Res.,. 53. 2944-2946 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nishigori,C.,et al.: "High prevalence of a point mutation in exon 6 of XPAC gene in xeroderma pigmentosum group A patients in Tunisia." American J.Human Genet.,. 53. 1001-1006 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takimoto,K.,et al.: "Spectrum of proton-induced mutagenesis of Escherichia colo crp gene." Mutation Res.,. 314. 1-9 (1994)

    • Related Report
      1993 Annual Research Report

URL: 

Published: 1993-03-31   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi