1998 Fiscal Year Annual Research Report

発がんの原因となる染色体異常に関する研究

Research Project

Project/Area Number	10151207
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)	加藤潤一東京大学, 医科学研究所, 助手 (10194820)
Keywords	非相同的組換え / 染色体異常 / DNA修復 / Ku抗原 / サイレンシング因子 / 染色体分配 / ウェルナー症候群 / ブルーム症候群
Research Abstract	近年、染色体異常とKu抗原遺伝子やSIR2,SIR3,SIR4などクロマチン構造と関連する遺伝子との関連が明らかになりつつある。我々は、二本鎖切断されたDNA末端にKu抗原やサイレンシング因子が結合し、複合体を形成してエンドジョイニングに働くと考えているが、本研究ではこの複合体の機能にヒストンH4が関与すること、また、特殊のアセチル化酵素Natl-Ardlが必要であることを示した。さらに、出芽酵母SGS1遺伝子の破壊株では非相同的組換えによる欠失変異が起こる頻度が高い事を明らかにした。ブルーム症候群、ウェルナー症候群原因遺伝子を出芽酵母の中で発現させSGS1の欠損を相補できるかどうかについて調べ、この二つの遺伝子が出芽酵母において非相同的組換えを抑制する機能を持つことを示した。出芽酵母Rhc21遺伝子産物cohesinは、S期に複製された姉妹染色体分体同士をM期中期までつなぎとめることで未成熟な染色体分配を抑え、正常なmitosis進行をさせる働きをしている。rhc21変異株の多コピーサプレッサーの解析から、PKA、CDC28などのリン酸化酵素やユビキチン経路の制御因子であるCDC20と遺伝的相互作用があることが明らかになり、その機能が複雑な制御をうけていることが予想された。興味深いことに、RHC21遺伝子は、体細胞分裂期での染色体分配に加えて、相同的組換えや減数分裂にも重要な機能をもつことが示唆された。以上の結果から、RHC21蛋白質は正常な染色体分配を維持する役割に加えて、組換えや胞子形成などの様々な染色体機能に関与すると考えられる。

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 hy perrecombination in yeast sgs1 mutant Implication for genomlc 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 Furuichi,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." 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

発がんの原因となる染色体異常に関する研究

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 hy perrecombination in yeast sgs1 mutant Implication for genomlc 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 Furuichi,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." 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)