1999 Fiscal Year Annual Research Report

活性酸素DNA損傷修復酵素欠損と突然変異

Research Project

Project/Area Number	11146201
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)	久保喜平大阪府立大学, 農学部, 教授 (40117619) 布柴達男東北大学, 大学院・理学研究科, 助教授 (10270802)
Keywords	チミングリコール / 自然突然変異 / オスミウム酸 / 5-ヒドロキシシトシン / leading鎖合成 / lagging鎖合成 / 8-oxoG / 8-oxo-dGTP
Research Abstract	大腸菌NKJ1004(nth nei)株中で複製させたsupF遺伝子を持つプラスミド、pTN89、の自然突然変異、オスミウム酸誘発突然変異を調べたところ、G:C→A:T変異が高い頻度で生じていた。A:T塩基対では変異は増加していない。nth nei二重欠損株は、チミングリコールや5-ヒドロキシシトシンの修復欠損である。オスミウム酸は高い頻度でチミングリコールを作ることが知られている。従って、チミングリコールには変異原性はないと結論することが出来る。G:C→A:T変異の原因損傷については、5-ヒドロキシシトシンなどのシトシン損傷が関係している可能性がある。つぎに、これらの変異生成がDNA複製の1eading鎖合成、lagging鎖合成に影響されるかどうかを調べた。使用したのは、mutM mutY二重変異株で、この株ではDNAにできた8-oxoGの修復は全く見られない。supF遺伝子の複製方向が別である2種のプラスミドを作り、mutM mutY株での自然突然変異を調べたところ、変異頻度においても、変異の場所においても、2つのプラスミドでは差は認められなかった。同様に2種のプラスミドをmutT欠損株で調べたところ、変異頻度も変異のスペクトルでも差はなかった。mutT株ではヌクレオチドプール中の8-oxo-dGTPは取り除かれない。従って、DNA複製の時に異常塩基を鋳型にしたり、異常塩基を取り込む際に、1agging鎖合成でも、leading鎖合成でも同じ程度の忠実性であることが分かった。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Tatsuo Nunoshiba: "Role of iron and superoxide for gereration 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 po[A] 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"Enviromental 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DNA損傷修復酵素欠損と突然変異

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 gereration 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 po[A] 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"Enviromental 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)