1999 Fiscal Year Annual Research Report

活性酸素性の塩基損傷の認識と処理に関わる酵素群

Research Project

Project/Area Number	11138208
Research Institution	Tohoku University
Principal Investigator	山本和生東北大学, 大学院・理学研究科, 教授 (20093536)
Co-Investigator(Kenkyū-buntansha)	布柴達男東北大学, 大学院・理学研究科, 助教授 (10270802)
Keywords	酸化塩基 / 8-oxo-dGTP / mutT遺伝子 / 酵母 / MutTホモローク / mutator / GST融合タンパク質
Research Abstract	大腸菌の場合ヌクレオチドプール中の酸化塩基である8-oxo-dGTPの除去には、mutTおよびribA遺伝子産物が関わっていることが明らかになった。ribA遺伝子がコードするリボフラビン合成系の酵素GTP cyclohydrolase II(GCHII)は、GTPを基質にするほかに、8-oxo-dGTPや8-oxo-rGTPを分解して、8-oxo-dGMPや8-oxo-rGMPにすることで、酸化塩基の変異原性を取り除いている。同様の作用をする遺伝子の有無を酵母の遺伝子ライブラリーの中から検索したところ、現在までに1つのクローンを得た。このクローンについて、 1)全体のアミノ酸配列は大腸菌MutTタンパク質とは相同性はない。ただし、MutTの活性に関わるMutT box類似の配列がある。 2)クローニングした酵母の断片を、大腸菌mutT欠損株に入れると、部分的に大腸菌のmutT欠損を相補する。 3)遺伝子破壊株は弱いmutator活性を持つ。またGST融合タンパク質として遺伝子産物を精製し、in vitroで8-oxo-dGTP分解活性の有無を調べるところである。ヒトやマウスのMutT homologであるMTHをdisruptしてやっても、8-oxo-dGTP分解活性は完全には低下しない。このことより、MutTのbackup systemが存在すると想定される。今回我々がクローニングした遺伝子のhomologが高等真核生物でも存在するかどうかも重要な問題である。

Research Products
(12 results)

All Other

All Publications (12 results)

[Publications] Tatsuo Nunoshiba: "Role of iron and superoxide for generation of hydroxyl radical,oxidative DNA lesions and mutagenesis in Escherichia coli"J.Biol.Chem.. 274. 34832-34837 (1999)
[Publications] Norio Uematsu: "Asymmetric crossover for spontaneous formation of large deletions at the tonB-trp region of Escherichia coli K-12 cells"Mol.Gen.Genet. 261. 523-529 (1999)
[Publications] Tomoo Funayama: "Deinococcus radiodurans recN gene : A molecular analysis of mitomycin-C sensitive strain and gene"Mutation Res.. 435. 151 (1999)
[Publications] Hiroaki Iyehara-Ogawa: "Cobaltous chloride-induced mutagenesis in the supF tRNA gene of Escherichia coli"Mutagenesis. 14. 249-253 (1999)
[Publications] Tatsuo Nunoshiba: "Role of glutathione on acrolein-induced cytotoxicity and mutagenicity in Escherichia coli"Mutation Res.. 442. 1-8 (1999)
[Publications] Yumi Agemizu: "DNA sequence analysis of spontanous tonB deletion mutations in a polAI strain of Escherichia coli K12"Biochem.Biophys.Res.Commun. 261. 584-589 (1999)
[Publications] Masahiro Kikuchi: "Genomic organization of the extraordinary radioresistant bacterium Deinococcus radiodurans : physical map and evidence for multiple replicons"FEMS Microbiol.Letters. 174. 151-157 (1999)
[Publications] Tetsuya Ono: "Molecular nature of mutation induced by high dose of X-ray in spleen,liver and brain of the lacZ-transgenic mouse"Environmental and Molecular Mutagenesis. 34. 97-105 (1999)
[Publications] Issay Narumi: "Molecular analysis of Deinococcus radiodurans recA locus and identification of a mutation site in a DNA-repair deficient mutant rec30"Mutation Res.. 435. 233-243 (1999)
[Publications] Tanbir Najrana: "Spontaneous and osmium tetroxide induced mutagenesis in Escherichia coli strain deficient both endonuclease III and endonuclease VIII"Mutagenesis. (印刷中). (1999)
[Publications] Tetsuya Ono: "Age-associated increase of spontaneous mutation frequency and molecular nature of mutation in newborn and old lacZ-transgenic mouse"Mutation Res.. (印刷中). (1999)
[Publications] Shingo Nakamura: "Radiation-induced mutation in spleen and brain of lacZ transgenic mouse"Int.J.Radiat.Biol.. (印刷中). (1999)

1999 Fiscal Year Annual Research Report

活性酸素性の塩基損傷の認識と処理に関わる酵素群

Principal Investigator

山本 和生 東北大学, 大学院・理学研究科, 教授 (20093536)

Research Products

[Publications] Tatsuo Nunoshiba: "Role of iron and superoxide for generation of hydroxyl radical,oxidative DNA lesions and mutagenesis in Escherichia coli"J.Biol.Chem.. 274. 34832-34837 (1999)

[Publications] Norio Uematsu: "Asymmetric crossover for spontaneous formation of large deletions at the tonB-trp region of Escherichia coli K-12 cells"Mol.Gen.Genet. 261. 523-529 (1999)

[Publications] Tomoo Funayama: "Deinococcus radiodurans recN gene : A molecular analysis of mitomycin-C sensitive strain and gene"Mutation Res.. 435. 151 (1999)

[Publications] Hiroaki Iyehara-Ogawa: "Cobaltous chloride-induced mutagenesis in the supF tRNA gene of Escherichia coli"Mutagenesis. 14. 249-253 (1999)

[Publications] Tatsuo Nunoshiba: "Role of glutathione on acrolein-induced cytotoxicity and mutagenicity in Escherichia coli"Mutation Res.. 442. 1-8 (1999)

[Publications] Yumi Agemizu: "DNA sequence analysis of spontanous tonB deletion mutations in a polAI strain of Escherichia coli K12"Biochem.Biophys.Res.Commun. 261. 584-589 (1999)

[Publications] Masahiro Kikuchi: "Genomic organization of the extraordinary radioresistant bacterium Deinococcus radiodurans : physical map and evidence for multiple replicons"FEMS Microbiol.Letters. 174. 151-157 (1999)

[Publications] Tetsuya Ono: "Molecular nature of mutation induced by high dose of X-ray in spleen,liver and brain of the lacZ-transgenic mouse"Environmental and Molecular Mutagenesis. 34. 97-105 (1999)

[Publications] Issay Narumi: "Molecular analysis of Deinococcus radiodurans recA locus and identification of a mutation site in a DNA-repair deficient mutant rec30"Mutation Res.. 435. 233-243 (1999)

[Publications] Tanbir Najrana: "Spontaneous and osmium tetroxide induced mutagenesis in Escherichia coli strain deficient both endonuclease III and endonuclease VIII"Mutagenesis. (印刷中). (1999)

[Publications] Tetsuya Ono: "Age-associated increase of spontaneous mutation frequency and molecular nature of mutation in newborn and old lacZ-transgenic mouse"Mutation Res.. (印刷中). (1999)

[Publications] Shingo Nakamura: "Radiation-induced mutation in spleen and brain of lacZ transgenic mouse"Int.J.Radiat.Biol.. (印刷中). (1999)

山本和生東北大学, 大学院・理学研究科, 教授 (20093536)