1998 Fiscal Year Annual Research Report

DNA二本鎖切断の際に染色体末端で形成されるエンドジョイニング複合体の構造と機能

Research Project

Project/Area Number	10159204
Research Institution	The University of Tokyo
Principal Investigator	池田日出男東京大学, 医科学研究所, 教授 (10012775)
Co-Investigator(Kenkyū-buntansha)	塚本恭正東京大学, 医科学研究所, 学振特別研究員
Keywords	DNA二本鎖切断 / DNAエンドジョイング / サイレンシング因子 / Mrell / Ku抗原 / ヒストンアセチル化 / クロマチン / テロメア
Research Abstract	我々は、DNA二本鎖切断によって形成されるDNA末端のエンドジョイニングの際に形成されるDNA-蛋白質複合体に含まれる因子を探索する目的で解析を行い、ヒストンH4やヒストンアセチル化酵素Nat1-Ard1が、DNAのエンドジョイニングに働き、その機構を通して欠失変異を引き起こす非相同的組換えや修復に関与していることを明らかにした。これらの結果を基にして、DNAの末端が凝縮してヘテロクロマチン様の構造を形成するというモデルを提唱した。さらに、出芽酵母Sgs1ヘリケースが相同的組換えを介して非相同的組換えを抑制することを明らかにした。さらに、出芽酵母Sgs1ヘリケース遺伝子をBLM及びWRNへリケース遺伝子と置き換えた酵母株を作成して、酵母細胞内でのBLM及びWRNヘリケースの働きを調べ、BLM及びWRNヘリケースが酵母において相同的組換えを介して非相同的組換えを抑制することを示した。次に、姉妹染色体をつなぐ役割をするcohesinに関わる因子を明らかにする目的で、分裂酵母Rad21pと相互作用する因子をtwo-hybrid systemを用いて探索した。その結果、分裂酵母の新規遺伝子toil^+を単離した。toil^+遺伝子の解析の結果、toil^+が細胞のM期から間期への移行に必須であることを示した。またtoil^+と遺伝学的に相互作用する遺伝子として分裂酵母のRanGTPaseであるspil^+が単離されたことから、toil^+がRanGTPase systemに働くことが強く示唆された。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Heo,S.-J.,Tatebayashi,K.,Kato,J.,and Ikeda,H.: "Budding yeast RHC21 gene,a homologue of fission yeast rad21^+ gene,is essential for chromosome segregation." Mol.Gen.Genet.257. 149-156 (1998)
[Publications] Yamagata,K.,Kato,J.,Shimamoto,A.,Goto,M.,Furuichi.Y.,and Ikeda,H.: "Bloom's and Werner's syndrome genes suppress hyperrecombination in yeast sgs1 mutant Implication for genomic instability in human diseases." Proc.Natl.Acad.Sci.USA. 95. 8733-8738 (1998)
[Publications] Sato,Y.,Shimamoto,A.,Shobuike,T.,Sugimoto,M.,Ikeda,H.,Kuroda,S.and Furiichi,Y.: "Cloning and characterization of human Sep1(hSEP1) gene and cytoplasmic localization of its product." DNA Res.5. 241-246 (1998)
[Publications] Shanado,Y.,Kato,J.and Ikeda,H.: "Escherichia coli HU protein suppresses DNA-gyrase-mediated illegitimate recombination and SOS induction." Genes Cells. 3. 511-520 (1998)
[Publications] Tsukamoto,Y.and Ikeda,H.: "Double-strand break repair mediated by DNA end-joining." Genes Cells. 3. 135-144 (1998)
[Publications] Onda,M.,Hanada,K.,Kawachi,H.and Ikeda,H.: "Escherichia coli MutM suppresses illegitimate recombination induced by oxidative stress." Genetics. 151. 439-446 (1999)
[Publications] Tatebayashi,K.,Kato,J.,and Ikeda,H.: "Isolation of a Schizosaccharomyces pom be rad21ts muatnt which is aberrant in chromosome segregation,microtubule function,DNA repair and DNA replication:possible involvement of Rad21 in ubiquitin-mediated proteolysis" Genetics. 148. 49-57 (1998)
[Publications] A.Hasebe,S.Tsushima and S.Iida: "Isolation and characterization of IS1416 from Pseudomonas glumae,an new member of the IS3 family" Plasmid. 39. 196-204 (1998)
[Publications] S.Iida,: "1998 Accessory genes in the darA operon of bacteriophage P1 affect anti-restriction function,generalized transduction,head morphogenesis and host cell lysis" Virology. 251. 49-58 (1998)
[Publications] Y.Habu,Y.Hisatomi and S.Iida: "Molecular characterization of the mutable flaked allele for flower variegation in the common morning glory." Plant J.16. 371-376 (1998)
[Publications] Y.Inagaki,: "Genomic organization of the genes encoding dihydroflavonol 4-reductase for flower pigmentation in the Japanese and common morning glories" Gene. (In press).
[Publications] S.Takahashi,: "Capturing of a genomic HMG domain sequence by an En/Spm related transposable element Tpn 1 in the Japanese morning glory" Mol.Gen.Genet.(In press).

1998 Fiscal Year Annual Research Report

DNA二本鎖切断の際に染色体末端で形成されるエンドジョイニング複合体の構造と機能

Principal Investigator

池田 日出男 東京大学, 医科学研究所, 教授 (10012775)

Research Products

[Publications] Heo,S.-J.,Tatebayashi,K.,Kato,J.,and Ikeda,H.: "Budding yeast RHC21 gene,a homologue of fission yeast rad21^+ gene,is essential for chromosome segregation." Mol.Gen.Genet.257. 149-156 (1998)

[Publications] Yamagata,K.,Kato,J.,Shimamoto,A.,Goto,M.,Furuichi.Y.,and Ikeda,H.: "Bloom's and Werner's syndrome genes suppress hyperrecombination in yeast sgs1 mutant Implication for genomic instability in human diseases." Proc.Natl.Acad.Sci.USA. 95. 8733-8738 (1998)

[Publications] Sato,Y.,Shimamoto,A.,Shobuike,T.,Sugimoto,M.,Ikeda,H.,Kuroda,S.and Furiichi,Y.: "Cloning and characterization of human Sep1(hSEP1) gene and cytoplasmic localization of its product." DNA Res.5. 241-246 (1998)

[Publications] Shanado,Y.,Kato,J.and Ikeda,H.: "Escherichia coli HU protein suppresses DNA-gyrase-mediated illegitimate recombination and SOS induction." Genes Cells. 3. 511-520 (1998)

[Publications] Tsukamoto,Y.and Ikeda,H.: "Double-strand break repair mediated by DNA end-joining." Genes Cells. 3. 135-144 (1998)

[Publications] Onda,M.,Hanada,K.,Kawachi,H.and Ikeda,H.: "Escherichia coli MutM suppresses illegitimate recombination induced by oxidative stress." Genetics. 151. 439-446 (1999)

[Publications] Tatebayashi,K.,Kato,J.,and Ikeda,H.: "Isolation of a Schizosaccharomyces pom be rad21ts muatnt which is aberrant in chromosome segregation,microtubule function,DNA repair and DNA replication:possible involvement of Rad21 in ubiquitin-mediated proteolysis" Genetics. 148. 49-57 (1998)

[Publications] A.Hasebe,S.Tsushima and S.Iida: "Isolation and characterization of IS1416 from Pseudomonas glumae,an new member of the IS3 family" Plasmid. 39. 196-204 (1998)

[Publications] S.Iida,: "1998 Accessory genes in the darA operon of bacteriophage P1 affect anti-restriction function,generalized transduction,head morphogenesis and host cell lysis" Virology. 251. 49-58 (1998)

[Publications] Y.Habu,Y.Hisatomi and S.Iida: "Molecular characterization of the mutable flaked allele for flower variegation in the common morning glory." Plant J.16. 371-376 (1998)

[Publications] Y.Inagaki,: "Genomic organization of the genes encoding dihydroflavonol 4-reductase for flower pigmentation in the Japanese and common morning glories" Gene. (In press).

[Publications] S.Takahashi,: "Capturing of a genomic HMG domain sequence by an En/Spm related transposable element Tpn 1 in the Japanese morning glory" Mol.Gen.Genet.(In press).

池田日出男東京大学, 医科学研究所, 教授 (10012775)