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

Mechanisms os spontaneous mutation and its control

Research Project

Project/Area Number 06102006
Research Category

Grant-in-Aid for Specially Promoted Research

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionFukuoka Dental College (1996)
Kyushu University (1994-1995)

Principal Investigator

SEKIGUCHI Mutsuo  Fukuoka Dental College, Dept. of Biology, Professor, 歯学部, 教授 (00037342)

Co-Investigator(Kenkyū-buntansha) SAKUMI Kunihiko  Kyusyu University, Medical Institute of Bioregulation, Research Associate, 生体防御医学研究所, 助手 (50211933)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥152,000,000 (Direct Cost: ¥152,000,000)
Fiscal Year 1996: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1995: ¥64,000,000 (Direct Cost: ¥64,000,000)
Fiscal Year 1994: ¥83,000,000 (Direct Cost: ¥83,000,000)
Keywordsspontaneous mutation / oxygen radical / gene-targeting / alkylating agent / cell death / carcinogenesis / DNA repair / oxidation / ノックアウトマウス / 突然変異 / メチルトランスフェラーゼ / ミューテーター / 8-oxodGTPase / 酸化型グアニン / ヌクレオチド代謝 / DNA合成 / ヌクレオチド / 突然変異制御 / 遺伝子クローニング / 染色体変異
Research Abstract

Mutator mutants that show an increased frequency of spontaneous mutation have led to the elucidation of the multiple pathwavs of spontaneous mutagenesis. 8-Oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate) is formed in the nucleotide pool of a cell during normal cellular metabolism, and when it is incorporated into DNA causee mutation. MutT protein of Escherichia coli and related mammalian enzymes specifically degrade 8-oxo-dGTP to 8-oxo-dGMP,thereby preventing occurrence of transversion mutation. The gene encoding the human enzyme, designated MTH1 (for mutT homologue 1), maps to chromosome 7p22. To elucidate the roles of 8-oxo-dGPTase in carcinogenesis, it is necessary to construct an animal model with altered levels of the enzyme activity. It is interest to determine whether the frequency of occurrence of tumors would increase in mice defective in the 8-oxo-dGTPase gene. For this, we isolated the genomic sequence for mouse 8-oxo-dGTPase peotein, identified the exon/intron region of the gene, and characterized the promoter in relation to the regulation of expression of the gene.
Alkylation of DNA at the O^6-position of guanine is one of the most critical events leading to induction of mutation as well as to cancer. The enzyme O^6-methylguanine-DNA methyltransferase repairs this and related lesions in DNA.By means of gene targeting, we established mouse lines deficient in the methyltransferase gene and tissues from these mice contained no methyltransferase activity. Administration of methylnitrosourea to these gene-targeted mice led to early death, and normal mice treated in the same manner showed no untoward effects. In mice given methylnitrosourea treatment, the bone marrow became hypocellular and there was a drastic decrease in the number of leukocytes and platelets, thereby indicating an impaired reproductive capacity of hematopoietic stem cells. Methyltransferase apparently protected these mice from the pnacytopenia caused by the alkylating agent.

Report

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

    (99 results)

All Other

All Publications (99 results)

  • [Publications] Ishibashi,T.: "Intracellular localization and function of DNA repair methyltransferase in human cells" Mutation Res.315・3. 199-212 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Furuichi,M.: "Genomic structure and chromosome location of the human mutT homologue gene MTH1 encoding 8-oxo-d GTP nse for prevention of A : T to C : G trunsversion." Genomics.24・3. 485-490 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ihara,K.: "Requirement of the Pro-Cys-Ilis-Arg sequence for O^6-methyl-guanine-DNA methyltransferase netivity revenled by saturation mutngenesis with negntive and positive soreening" Molec.Gen.Genet.243・4. 379-389 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ishibashi,T.: "Artifieial control of nuclear translocation of DNA repair methy Itransferase" J.Biol.Chem.269・10. 7645-7650 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito,M.: "Metastatic phenotype in hybrid cells derived from B16 melanoma." Cancer Letters.78・1-3. 33-39 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito,T.: "Roles of transcription and repair in alky latron mutagenesis" Mutation Res.314・3. 273-285 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iyama,A.: "A unique structural feuture of rabbit rapair methyl-transferase as revealed by cDNA cluning" Carcinogenesis. 15・4. 627-633 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ohkubo,T.: "Methylation dependent functionul switch mechunism newly found in the Escherichia coli Actn protein" J.Am.Chem.Soc.116. 6035-6036 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Belguise-Valladier: "Effect of single DNA lesions on in vitro replication with DNA polymerase III holornzyme. Comparison with other polymerase" J.Mol.Biol.236・1. 151-164 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cai,J.P.: "cDNA and genomic sequences for rat 8-oxo-dGTP ase that prevents occurrence of spontaneous mutations due to oxidation of guanice nucleotide" Carcinogenesis.16・10. 2343-2350 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hayakawa,H.: "Generation and elimination of 8-oxo-7,8-dihydro-2′-deoxy-guanosine 5′-triphosphace, a mutagenic substrute for DNA synthesis, in human cells" Biochemistry.34・1. 89-95 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kakuma,T.: "Mouse MTH1 protein with 8-oxo-dGTP ase activity that prevents transversion mutution. cDNA cloning and tissue distribntion" J.Biol.Chem.270・43. 25942-25948 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kang,D.: "Intracellular localizution of 8-oxo-dGTP ase in human cells, with special reference to the role of the enzyme in mitochoundria" J.Biol.Chem.270・24. 14659-14665 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kawata,H.: "Mouse methyltransferase for repiar of O^6-methylguanine and O^4-methylthymine in DNA" Carcinogenesis.16・7. 1595-1602 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Oda,S.: "Stabilization of cyclin E and Ctlk2 mRNAs at the Gl-S trunstion in rat-1A cells emerged from the Go stute" Oncogene.10・7. 1343-1351 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sakashita,H.: "Sequence-specilic DNA recognition of the Escherichia coli Acla protein associated with the methylution-dependent functionol switch for transcriptional regulution" J.Biochem.118・6. 1184-1191 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tajiri.T.: "Functional couperation of MutT, MutM and MutY proteins in preventing mutations caused by spontaneous oxidution of guanine nucelotide in Escherichia coli" Mutation Res.336・3. 257-267 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka,K.: "Cyclic AMP-mediated synthesis of the tissue inhibitors of metalloproteinases supresses the invasive potentiul of the human fibrosurcoma cell line,IIT1080" Cancer Res.55・13. 2927-2935 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Wu,C.: "Polymorphisms and probable lack of mutation in a human mutT homolog,hMTH1, in hereditary nonpoliposis colorectul cancer." Biochem. Biophys. Res. Comm.214・3. 1239-1245 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Bridges,B.A.: "Effect of mutY and mutM llpg-1 mutations on starvation-associated mutation in erichia coli : implicutions for the role of 7,8-dihydro-8-oxoguanine" Molec. Gen. Genet.251・3. 352-357 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Otsuka,M.: "Polymorphism in the human O^6-methylgnanine-DNA methylitransferase gene detected by PCR-SSCP unulysis" Pharmacogenetics.6. 361-363 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Taketomi,A.: "Requirement of two conserved cysteine residues of Ada protein of Escherichia coli for trunsuctivution of ada promoter" Mol. Gen. Genet.250・5. 523-532 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ishibashi, T., Nakabeppu, Y., Kawate, H., Sakumi, K., Hayakawa, H.and Sekiguchi, M: "Intracellular locelization and function of DNA repair methyltransferase in human cells." Mutation Res.315 (3). 199-212 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Furuichi, M., Yoshida, M.C., Oda, H., Tajiri, T., Nakabeppu, Y., Tsuzuki, T.and Sekiguchi, M.: "Genomic structure and chromosome location of the human mutT homologue gene MTHl encoding 8-oxo-dGTPase for prevention of A : T to C : G transversion." Genomics.24 (3). 485-490 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ihara, K., Kawate, H., Chueh, L.L., Hayakawa, H.and Sekiguchi: "M. : Requirement of the Pro-Cys-His-Arg sequence for O^6-methyl-guanine-DNA methyltransferase activity revealed by saturation mutagenesis with negative and positive screening." Molec. Gen. Genet. 243 (4). 379-389 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ishibashi, T., Nakabeppu, Y., and Sekiguchi, M.: "Artificial control of nuclear translocation of DNA repair methyltansferase." J.Biol. Chem.269 (10). 7645-7650 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito, M., Izuhara, M., Shimizu, K.and Sekiguchi, M.: "Metastatic phenotype in hybrid cells derived from B16 melanoma." Cancer Letters. 78 (1-3). 33-39 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito, T., Nakamura, T., Maki, H.and Sekiguchi, M.: "Roles of transcription and repair in alkylation mutagenesis." Mutation Res.314 (3). 273-285 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iyama, A., Sakumi, K., Nakabeppu, Y.and Sekiguchi, M.: "A unique structural feature of rabbit repair methyl-transferase as revealed by cDNA cloning." Carcinogenesis. 15 (4). 627-633 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ohkubo, T., Sakashita, H., Sakuma, T., Kainosho, M., Sekiguchi, M.and Morikawa, K.: "Methylation dependent functional switch mechanism newly frond in the Escherichia coli Ada protein." J.Am. Chem. Soc.116. 6035-6036 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] P.Belguise-Valladier. P., Maki, H., Sekiguchi, M.and Fuchs, R.P.: "Effect of single DNA lesions on in vitro replication with DNA polymerase III holoenzyme. Comparison with other polymerase." J.Mol. Biol.236 (1). 151-164 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cai, J.P., Kakuma, T., Tsuzuki, T.and Sekiguchi, M.: "cDNA and genomic sequences for rat 8-oxo-dGTPase that prevents occurrence of spontaneous mutations due to oxidation of guanine nucleotide." Carcinogenesis.16 (10). 2343-2350 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hayakawa, H., Taketomi, A., Sakumi, K., Kuwano, M.and Sekiguchi, M.: "Generation and elimination of 8-oxo-7,8-dihydro-2'-deoxy-guanosine 5'-triphosphate, a mutagenic substrate for DNA synthesis, in human cells." Biochemistry.34 (1). 89-95 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kakuma, T., Nishida, J., Tsuzuki, T.and Sekiguchi, M.: "Mouse MTHl protein with 8-oxo-dGTPase activity that prevents transyersion mutation. cDNA cloning and tissue distribution." J.Biol. Chem.270 (43). 25942-25948 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kang, D., Nishida, J., Iyama, A., Nakabeppu, Y., Furuichi, M., Fujiwara, T., Sekiguchi, M.and Takeshige, K.: "Intracellular localization of 8-oxo-dGTPase in human cells, with special reference to the role of the enzyme in mitochondria." J.Biol. Chem.270 (24). 14659-14665 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kawate, H., Ihara, K., Kohda, K., Sakumi, K.and Sekiguchi, M.: "Mouse methyltransferase for repiar of O^6-methylguanine and O^4-methylthymine in DNA." Carcinogenesis.16 (7). 1595-1602 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Oda, S., Nishida, J., Nakabeppu, Y.and Sekiguchi, M.: "Stabilization of cyclin E and Cdk2 mRNAs at the Gl-S transtion in rat-lA cells emerged from the Go state." Oncogene.10 (7). 1343-1351 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sakashita, H., Sakuma, T., Akitomo, Y., Ohkubo, T., Kainosho, M., Sekiguchi, M.and Mokikawa, K.: "Sequence-specific DNA recognition of the Escherichia coli Ada protein associated with the methlyation-dependent functional switch for transcriptional regulation." J.Biochem.118 (6). 1184-1191 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tajiri, T., Maki, H.and Sekiguchi, M.: "Functional cooperation of MutT,MutM and MutY proteins in preventing mutations caused by spontaneous oxidation of guanine nucelotide in Escherichia coli." Mutation Res.336 (3). 257-267 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka, K., Iwamoto, Y., Ito, Y., Ishibashi, T., Nakabeppu, Y., Sekiguchi, M.and Sugioka, Y.: "Cyclic AMP-midiated synthesis of the tissue inhibitors of metalloproteinases suppresses the invasive potential of the human fibrosarcoma cell line, IIT1080." Cancer Res.55 (13). 2927-2935 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Wu, C., Nagasaki, H., Maruyama, K., Nakabeppu, Y., Sekiguchi, M.and Yuasa, Y.: "Polymorphisms and probable lack of mutation in a human mutT homolog, hMTH1, in hereditary nonpoliposis colorectal cancer." Biochem. Biophys. Res. Comm.214 (3). 1239-1245 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Bridges, B.A., Sekiguchi, M.and Tajiri, T.: "Effect of mutY and mutM/fpg-1 mutations on starvation-associated mutation in Esherichia coli : implications for the role of 7,8-dihydro-8-oxoguanine." Molec. Gen. Genet.251 (3). 352-357 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Otsuka, M., Abe, M., Nakabeppu, Y., Sekiguchi, M.and Suzuki, T.: "Polymorphism in the human O^6-methylgnanine-DNA methyltransferase gene detected by PCR-SSCP analysis." Pharmacogenetics.6. 361-363 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Taketomi, A., Nakabeppu, Y., Ihara, K., Hart, D.J., Furuichi, M.and Sekiguchi, M.: "Requirement of two conserved cysteine residues of Aba protein of Escherichia coli for transactivation of ada promoter." Mol. Gen. Genet.250 (5). 523-532 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwakuma, T., Shiraishi, A., Fukuhara, M., Kawate, H.and Sekiguchi, M.: "Organization and expression of the mouse gene for DNA repair methyltransferase." DNA Cell Biol.15. 863-872 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsuzuki, T., Sakumi, K., Shiraishi, A., Kawate, H., Igarashi, H., Iwakuma, T., Tominaga, Y., Zhang, S., Shimizu, S., Ishikawa, K., Nakamura, K., Nakao, K., Katsuki, M.and Sekiguchi, M.: "Targeted disruption of the methyltransferase gene renders mice extraordinary sensitive to alkylating carcinogens." Carcinogenesis.17. 1215-1220 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsuzuki, T., Fujii, Y., Sakumi, K., Tominaga, Y., Nakao, K., Sekiguchi, M., Matsushiro, A., Yoshimura, Y.and Morita, T.: "Targeted disruption of the Rad51 gene leads to lethality in embryonic mice" Proc. Natl. Acad. Sci, U.S.A.93 (13). 6236-6240 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yamagata, Y., Kato, M., Odawara, K., Tokuno, Y., Nakashima, Y., Matsushima, N., Yasumura, K., Tomita, K., Ihara, K., Fujii, Y., Nakabeppu, Y., Sekiguchi, M.and Fujii, S.: "Three-dimentional structure of a DNA repair enzyme, 3-methyladenine DNA glycosylase II,from Escherichia coli." Cell.86 (2). 311-319 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Igarashi, II., Tsuzuki, T., Kabuma, T., Tominaga, Y.and Sekiguchi, M.: "Organization and expression of the mouse MTHl gene for preventing transversion mutation." J.Biol. Chem.272. 3766-3772 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwakuma, T., Sakumi, K., Nakatsuru, Y., Kawate, H., Igarashi, H., Shiraishi, A., Tsuzuki, T., Ishikawa, T.and Sekiguchi, M.: "High incidence of nitrosamine-induced tumorigenesis in mice lacking DNA repair methyltransferase." Carcinogenesis. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tominaga, Y., Tsuzuki, T., Shiraishi, A., Kawate, H.and Sekiguchi, M: "Alkylation-induced apoptosis of embryonic stem cells in which the gene for DNA repair methyltransferase had been disrupted by gene targeting." Carcinogenesis. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Cai, J.-P., Kawate, H., Ihara, K., Yakushiji, H., Nakabeppu, Y., Tsuzuki, T.and Sekiguchi, M.: "Significance of the conserved amino acid sezuence for human MTHl protein with antimutator activity." Nucleic Acids Res. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sakumi, K., Shiraishi, A., Shimizu, S., Tsuzuki, T., Ishikawa, T.and Sekiguchi, M.: "Methylnitrosovrea-induced tumorigenesis in MGMT gene-knockoyut mice." Cancer Res.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ishibashi,T.: "Intracellular localization and function of DNA repair methyltransferase in human cells" Mutation Res.315・3. 199-212 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Furuichi,M.: "Genomic structure and chromosome location of the human must T homologue gene MTH1 encoding 8-oxo-dGTPase for prevention of A : T to C : G transversion." Genomics.24・3. 485-490 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ihara,K.: "Requirement of the Pro-Cys-His-Arg sequence for O^6-methyl-guanine-DNA methyltransferase activity revealed by saturation mutagenesis with negative and positive screening" Molec.Gen.Genet.243・4. 379-389 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ishibashi,T.: "Artificial control of nuclear translocation of DNA repair methyltransferase" J.Biol.Chem.269・10. 7645-7650 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ito,M.: "Metastatic phenotype in hybrid cells derived from BIG melanoma." Cancer Letters.78・1-3. 33-39 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ito,T.: "Roles of transcription and repair in alkylation mutagenesis" Mutation Res.314・3. 273-285 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Iyama,A.: "A unique structural feature of rabbit repair methyl-transferase as revealed by cDNA cloning" Carcinogenesis. 15・4. 627-633 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ohkubo,T.: "Methylation dependent functional switch mechanism newly found in the Escherichia coli Ada protein" J.Am.Chem.Soc.116. 6035-6036 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Belguise-Valladier: "Effect of single DNA lesions on in vitro replication with DNA polymerase III holoenzyme. Comparison with other polymerase" J.Mol.Biol.236・1. 151-164 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Cai,J.P.: "cDNA and genomic sequences for rat 8-oxo-dGTPase that prevents occurrence of spontaneous mutations due to oxidation of guanine nucleotide" Carcinogenesis.16・10. 2343-2350 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hayakawa,H.: "Generation and elimination of 8-oxo-7,8-dihydro-2'-deoxy-guanosine 5'-triphosphate,a mutagenic substrate for DNA synthesis,in human cells" Biochemistry.34・1. 89-95 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kakuma,T.: "Mouse MTH1 protein with 8-oxo-dGTPase activity that prevents transversion mutation. cDNA cloning and tissue distribution" J.Biol.Chem.270・43. 25942-25948 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kang,D.: "Intracellular localization of 8-oxo-dGTPase in human cells,with special reference to the role of the enzyme in mitochondria" J.Biol.Chem.270・24. 14659-14665 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kawate,H.: "Mouse methyltransferase for repiar of O^6-methylguanine and O^4-methylthymine in DNA" Carcinogenesis.16・7. 1595-1602 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Oda,S.: "Stabilization of cyclin E and Cdk2 mRNAs at the Gl-S transtion in rat-lA cells emerged from the Go state" Oncogene.10・7. 1343-1351 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sakashita,H.: "Sequence-specific DNA recognition of the Escherichia coli Ada protein associated with the methylation-dependent functional switch for transcriptional regulation" J.Biochem.118・6. 1184-1191 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tajiri,T.: "Functional cooperation of MutT,MutM and MutY proteins in preventing mutations caused by spont-aneous oxidation of guanine nucelotide in Escherichia coli" Mutation Res.336・3. 257-267 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka,K.: "Cyclic AMP-mediated synthesis of the tissue inhibitors of metalloproteinases supresses the invasive potential of the human fibrosarcoma cell line,HT1080" Cancer Res.55・13. 2927-2935 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Wu,C.: "Polymorphisms and probable lack of mutation in a human mutT homolog,hMTH1,in hereditary nonpoliposis colorectal cancer." Biochem.Biophys.Res.Comm.214・3. 1239-1245 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Bridges,B.A.: "Effect of mutY and mutM lfpg-1 mutations on starvation-associated mutation in erichia coli : implications for the role of 7,8-dihydro-8-oxoguanine" Molec.Gen.Genet.251・3. 352-357 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Otsuka,M.: "Polymorphism in the human O^6-methylgnanine-DNA methyltransferase gene detected by PCR-SSCP analysis" Pharmacogenetics.6. 361-363 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Taketomi,A.: "Requirement of two conserved cysteine residues of Ada protein of Escherichia coli for transactivation of ada promoter" Mol.Gen.Genet.250・5. 523-532 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Iwakuma,T.: "Organization and expression of the mouse gene for DNA repair methyltransferase" DNA Cell Biol.15. 863-872 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsuzuki,T.: "Targeted disruption of the methyltransferase gene renders mice extraordinary sensitive to alkylating carcinogens" Carcinogenesis.17. 1215-1220 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsuzuki,T.: "Targeted disruption of the Rad51 gene leads to lethality in embryonic mice" Proc.Natl.Acad.Sci,U.S.A.93・13. 6236-6240 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamagata,Y.: "Three-dimentional structure of a DNA repair enzyme,3-methyladenine DNA glycosylase II,from Escherichia coli" Cell.86・2. 311-319 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Igarashi,H.: "Organization and expression of the mouse MTH1 gene for preventing transversion mutation" J.Biol.Chem.272. 3766-3772 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Iwakuma,T.: "High incidence of nitrosamine-induced tumorigenesis in mice lacking DNA repair methyltransferase" Carcinogenesis. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Tominaga,Y.: "Alkylation-induced apoptosis of embryonio stem cells in which the gene for DNA repair methyltransferase had been disrupted by gene targeting" Carcinogenesis. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Cai,J.-P.: "Significance of the conserved amino acid sezuence for human MTH1 protein with antimutator activity" Nucleic Acids Res. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiroshi Hayakawa: "Generation and elimination of 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate, a mutagenic substrate for DNA synthesis, in human cells" Biochemistry. vol. 34. 89-95 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tetsuya Kakuma: "Mouse MTH1 protein with 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphatase activity that prevents transversion mutation" J. Biol. Chem.vol. 270. 25942-25948 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Jian-Ping Cai: "cDNA and genomic sequences for rat 8-oxo-dGTPase that prevents occurrence of spontaneous mutations due to oxidation of guanine nucleotides" Carcinogenesis. vol 16. 2343-2350 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Dongchon Kang: "Intracellular localization of 8-oxo-dGTPase in human cells, with special reference to the role of the enzyme in mitochondria" J. Biol. Chem.vol.270. 14659-14665 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hisaya Kawate: "Mouse methyltransferase for repair of O^6-methylguanine and O^4-methylthymine in DNA" Carcinogenesis. vol. 16. 1595-1602 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shinya Oda: "Stabilization of cyclin E and cdk2 mRNAs at G1/S transition in Rat-1A cells emerging from the G0 state" Oncogene. vol. 10. 257-267 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tatsurou Tajiri: "Functional cooperation of MutT, MutM and MutY proteins in preventing mutations caused by spontaneous oxidation of guanine nucleotide in Escherichia coli" Mutation Res.vol.336. 257-267 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kazuhiro Tanaka: "Cyclic AMP-mediated synthesis of the tissue inhibitors of metalloproteinases suppresses the invative potential of the human fibrosarcoma cell line, HT1080" Cancer Res.vol. 55. 2927-2935 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Chi Wu: "Mutations in the human MTH1 gene in hereditary nonpolyposis colorectal cancer" Biochem. Biophys. Res. Commun.vol. 214. 1239-1245 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yusaku Nakabeppu: "Molecular Biology and Biotechnologgy: A comprehensive Desk Reference" VCH Publishers Inc., 234-238 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Toru Ishibashi: "Artificial control of nuclear translocation of DNA repair methyltransferase21GC01:J.Biol.Chem." 269. 7645-7650 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takayasu Ito: "Roles of transcription and repair in alkylation mutagenesis" Mutation Res.314. 273-285 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Ihara: "Reauirement of the Pro-Cys-Mis-Arg sequence for O6-methylguanine-DNA methyltransferase activity revealed by saturation mutagenesis" Mol.Gen.Genet.243. 379-389 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Akihiro Ihara: "A unique structural feature of rabbit DNA rapair methyltransferase as revealed by cDNA cloning" Carcinogenesis. 15. 627-633 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Toru Ishibashi: "Intracellular localization and function of DNA repair methyltransferase in human cells" Mutation Res.315. 199-212 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masaki Ito: "Genetic dominance of metastatic potential of B16 melanoma cells" Cancer Letters. 78. 33-39 (1994)

    • Related Report
      1994 Annual Research Report

URL: 

Published: 1994-04-01   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi