DNA複製、組換えにカップルしたcohesion形成機構の解析

• Project/Area Number: 18058003
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tohoku University
• Principal Investigator: 関 政幸 Tohoku University, 大学院・薬学研究科, 准教授 (70202140)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥4,400,000 (Direct Cost: ¥4,400,000); Fiscal Year 2007: ¥2,200,000 (Direct Cost: ¥2,200,000); Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: Rmi1 / Sgs1 / Top3 / Ctf18 / Arp8 / Ino80 / 姉妹染色分体接着 / コヒーシン / sister chramatid cohesion / 出芽酵母 / 相同組換え / 染色体不分離

Research Abstract

出芽酵母Sgs1/Rmi1/Top3複合体のうち、rmilおよびtop3欠損株において姉妹染色体の接着(cohesion)に部分的な欠損が生じることをこれまでに明らかにしてきた(EMBO reports8,685-690,2007)。ヒトBLM/BLAP75/TOP3α複合体は酵母Sgs1/Rmi1/Top3複合体に相当し、前者は試験管内でdouble Holliday junctions(DHJ)を解離する活性を有することが報告されているこどから、この活性を介して複製多オーク近傍でchesion形成を促進するという考え方と、この活性の喪失によって生じる複製フォークの不安定性が二次的にcohesion形成の一部を阻害している可能性が考えられた。
最近になりBrownちのグループは、生存に必須でないが、その欠損により一部cohesion形成に欠損が観察される遺伝子群を2つのグループに分類することに成功した。そこでrmil変異株のcohesion欠損がいずれのグループに属するのか、あるいは新規グループなのか調べた。その結果、RmilはCtf18/Ctf8/Dcclを含むalternative RFC複合体および複製チェックポイントに関わるMrc1と同じグループに属し、一方Ctf4,Chll,Csm3とは異なるグループであることがあきらかとなった。rmil変異株のcohesion欠損の表現型はSGS1遺伝子破壊により抑制されることから(EMBO reports8,685-690,2007)、Sgs1/Rmi1/Top3複合体自体がCtf18経路の中でcohesion形成を行う機能を担うとは考えにくい。そこでrmi1欠損により複製フォーク上のDHJ様の構造が解消されずに生じた異常が、正常なCtf18経路を介したcohesion形成を阻害したと考え、その立証を試みている。

Research Products

• [Journal Article] Vertebrate WRNIP1 and BLM are required for efficient maintenance of genome stability (2008)
  • Author(s): Hayashi T, Seki M, Inoue E, Yoshimura A, Kusa Y, Tada S, Enomoto T
  • Journal Title: Genes Genet. Syst. 83 Pages: 95-100
  • NAID: 10024395708
  • Peer Reviewed
• [Journal Article] Analyses of functional interaction between RECQL1, RECQL5, and BLM which physically interact with DNA topoisomerase IIIa (2008)
  • Author(s): Otsuki M, Seki M, Inoue E, Abe T, Narita Y, Yoshimura A, Tada S, Ishii Y, Enomoto T
  • Journal Title: Biochim. Biophys. Acta. 1782 Pages: 75-81
  • Peer Reviewed
• [Journal Article] Functional interactions between BLM and XRCC3 in the cell (2007)
  • Author(s): Otsuki M, Seki M, Inoue E, Yoshimura A, Kato G, Yamanouchi S, Kawabe Y, Tada S, Shinohara A, Komura J, Ono T, Takeda S, Ishii Y, Enomoto T.
  • Journal Title: J. Cell Biol. 179 Pages: 53-63
  • Peer Reviewed
• [Journal Article] Ctf18 is required for homologous recombination-mediated double-strand break repair (2007)
  • Author(s): Ogiwara. H., Ohuchi, T., Ui, A., Tada, S., Enomoto, T., Seki, M.
  • Journal Title: Nucleic Acids Res. 35 Pages: 4989-5000
  • Peer Reviewed
• [Journal Article] Rmil, a member of the Sgsl-Top3 complex in budding yeast, contributesto sister chromatid cohesion (2007)
  • Author(s): Lai, M.S., Seki, M., Ui, A., Enomoto, T.
  • Journal Title: EMBO Rep. 8 Pages: 685-690
  • Peer Reviewed
• [Journal Article] Activation of a novel pathway involving Mmsl and Rad59 in sgsl cells (2007)
  • Author(s): Ui A, Seki M, Ogiwara H, Lai MS, Yamamoto K, Tada S, Enomoto T.
  • Journal Title: Biochem. Biophys. Res. Commun. 356 Pages: 1031-1037
  • Peer Reviewed
• [Journal Article] The INO80 complex is required for damage-induced recombination (2007)
  • Author(s): Kawashima S, Ogiwara H, Tada S, Harata M, Wintersberger U, Enomoto T, Seki M.
  • Journal Title: Biochem. Biophys. Res. Commun. 355 Pages: 835-841
  • Peer Reviewed
• [Journal Article] Possible involvement of RecQL4 in the repair of double-strand DNA breaks in Xenopusegg extracts (2007)
  • Author(s): Kumata Y, Tada S, Yamanada Y, Tsuyama T, Kobayashi T, Dong YP, Ikegami K, Murofushi H, Seki M, Enomoto T.
  • Journal Title: Biochim. Biophys. Acta. 1773 Pages: 556-564
  • Peer Reviewed
• [Journal Article] WRN counteracts the NHEJ pathway upon camptothecin exposure (2007)
  • Author(s): Otsuki M, Seki M, Kawabe Y, Inoue E, Dong YP, Abe T, Kato G, Yoshimura A, Tada S, Enomoto T.
  • Journal Title: Biochem. Biophys. Res. Commun. 355 Pages: 477-482
  • Peer Reviewed
• [Journal Article] WRN functions in a RAD18-dependent damage avoidance pathway (2007)
  • Author(s): Dong YP, Seki M, Yoshimura A, Inoue E, Furukawa S, Tada S, Enomoto T
  • Journal Title: Biol. Pharm. Bull. 30 Pages: 1080-1083
  • NAID: 110006278395
  • Peer Reviewed
• [Journal Article] Rad50 is involved in MMS-induced recombination between homologous chromosomes in mitotic cells. (2007)
  • Author(s): Tomizawa Y, Ui A, Onoda F, Ogiwara H, Tada S, Enomoto T, Seki M.
  • Journal Title: Genes Genet. Syst. 82 Pages: 157-160
  • NAID: 10024394124
  • Peer Reviewed
• [Journal Article] The INO80 chromatin remodeling complex functions in sister chromatid cohesion (2007)
  • Author(s): Ogiwara H, Enomoto T, Seki M.
  • Journal Title: Cell Cycle 6 Pages: 1090-1095
  • Peer Reviewed
• [Journal Article] Actin-related protein Arp4 functions in kinetochore assembly (2007)
  • Author(s): Ogiwara H, Ui A, Kawashima S, Kugou K, Onoda F, Iwahashi H, Harata M, Ohta K, Enomoto T, Seki M.
  • Journal Title: Nucleic Acids Res. 35 Pages: 3109-3117
  • Peer Reviewed
• [Journal Article] Role of Elg1 protein in double strand break repair (2007)
  • Author(s): Ogiwara, H., Ui, A., Enomoto, T., Seki, M.
  • Journal Title: Nucleic Acids Res. 35 Pages: 353-362
• [Journal Article] The INO80 complex is required for damage-induced recombination (2007)
  • Author(s): Kawashima S., Ogiwara H., Tada S., Harata, M., Wintersberger, U., Enomoto T., Seki, M.
  • Journal Title: Biochem. Biophys. Res. Commun. 355 Pages: 835-841
• [Journal Article] Bloom helicase and DNA topoisomerase IIIα are involved in the dissolution of sister chromatids (2006)
  • Author(s): Seki, M., Nakagawa, T., Seki, T., Kato, G., Tada, T., Takahashi, Y., Yoshimura, A., Kobayashi, T., Aoki, A., Otsuki, M., Habermann, F.A., Tanabe, H., Ishii, Y., Enomoto, T.
  • Journal Title: Mol. Cell. Biol. 26 Pages: 6299-6307
• [Journal Article] Ubc9 and Mms21 mediated sumoylation counteracts recombinogenic events at damaged replication forks (2006)
  • Author(s): Branzei, D., Sollier J., Liberi, G., Zhao, X, Maeda, D., Seki, M., Enomoto, T., Ohta, K., Foiani, M.
  • Journal Title: Cell 127 Pages: 509-522
• [Journal Article] BLM is an early responder to DNA double-strand breaks (2006)
  • Author(s): Karmakar, P., Seki, M., Kanamori, M., Hashiguchi, K., Ohtsuki, M., Murata, E., Inoue, E., Tada, S., Lan, L., Yasui, A., Enomoto, T.
  • Journal Title: Biochem. Biophys. Res. Commun. 348 Pages: 62-69
• [Journal Article] Mgs1 and Rad18/Rad5/Mms2 are required for survival of Saccharomyces cerevisiae mutants with novel temperature /cold sensitive alleles of the DNA polymerase δ subunit, Pol31 (2006)
  • Author(s): Davoodi Vijeh Motlagh, N., Seki, M., Branzei, D., Enomoto, T.
  • Journal Title: DNA Repair 5 Pages: 1459-1474
• [Presentation] Novel functions of budding yeast Sgsl, Top3, and Rmil during DNA replication (2007)
  • Author(s): 関 政幸
  • Organizer: Chromosome and Genome Stability & Instability
  • Place of Presentation: 大阪/千里ライフサイエンスセンター
  • Year and Date: 2007-11-08
• [Book] Reviews and Protocols in DT40 Research (2006)
  • Author(s): 関政幸/多田周右/榎本武美
  • Total Pages: 24
  • Publisher: Springer社