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Molecular mechanisms of generation of pleiotropic effects of recombination genes

Research Project

Project/Area Number 11101003
Research Category

Grant-in-Aid for Specially Promoted Research

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionIwate College of Nursing (2001-2003)
National Institute of Genetics (1999-2000)

Principal Investigator

OGAWA Tomoko  Iwate College of Nursing, Professor, 看護学科, 教授 (80028208)

Co-Investigator(Kenkyū-buntansha) SHINOHARA Akira  Osaka University, Protein Res.Inst., Professor, 蛋白質研究所, 教授 (00252578)
TSUKAMOTO Yasumasa  Iwate College of Nursing, Assistant Professor, 看護学科, 講師 (80341725)
OGAWA Hideyuki  Iwate College of Nursing, Professor, 看護学科, 学長 (70028207)
SHINOHARA Miki  Osaka University, Protein Res.Inst., Research Associate, 蛋白質研究所, 助手 (80335687)
田中 茂生  国立遺伝学研究所, 細胞遺伝研究系, 助手 (10281586)
太田 力  国立遺伝学研究所, 細胞遺伝研究系, 助手 (10290892)
Project Period (FY) 1999 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥274,900,000 (Direct Cost: ¥238,000,000、Indirect Cost: ¥36,900,000)
Fiscal Year 2003: ¥52,000,000 (Direct Cost: ¥40,000,000、Indirect Cost: ¥12,000,000)
Fiscal Year 2002: ¥52,000,000 (Direct Cost: ¥40,000,000、Indirect Cost: ¥12,000,000)
Fiscal Year 2001: ¥55,900,000 (Direct Cost: ¥43,000,000、Indirect Cost: ¥12,900,000)
Fiscal Year 2000: ¥50,000,000 (Direct Cost: ¥50,000,000)
Fiscal Year 1999: ¥65,000,000 (Direct Cost: ¥65,000,000)
Keywordsmelotic recombination / Mre11 / Rad5O / Xrs2 complex / DNA homology search by Rad51・Rad52 / Domain structure of Xrs2 / Tell-Mre11 checkpoint pathway / recombination specific helicase MER3 / Roles of rad52 in recombination / No need of Xrs2 in DNA damage repair / 制限酵素SceI / Xrs2のMre11結合領域 / 組換えDNA修復合成 / Sae2のドメイン構造 / Xrs20複合体foci / Rad51蛋白質 / Xrs2の機能ドメイン / テロメア長維持 / DNA二重鎖切断修復 / DNA複製フォークの再生 / テロメアG鎖の二次構造認識 / Mrell-Rad50-Xrs2複合体 / Tell-Mrellチェックポイント経路 / Mre11蛋白質の機能制御 / DNA傷害修復でのMre11の役割 / テロメアG-rich構造を認識するMre11 / Mre11のリン酸化の役割 / Mer3蛋白質 / Mer3の交叉型組換えと染色体分配の役割 / 減数分裂期組換 / DNA二重連鎖切断の修復 / Mre11,Rad50,Xrs2蛋白質 / RAD51の転写制御 / Mre11 DNA結合活性
Research Abstract

A recombination function is required for repair of DNA breakages, overcome of DNA replication-arrest at a DNA lesion and maintenance of telomere length. We are interested in how multiple functions are produced by a single recombination protein. We selected a Mre11/rad50/Xrs2 complex (MRX), Rad51 and Rad52 as representatives, and investigated mechanisms that give full play to their multiple functioning ability. The followings are main results obtained during this research term.
We analyzed domains of Xrs2 which control the functions of MRX, and found (1)Xrs2 binds to Mre11 with a 32 amino-acid domain (MBX) near the C-terminus, and transports Mre11 into the nucleus. (2)Xrs2 is no more required for DNA damage repair if Mre11 has been transported into the nucleus. (3)For telomere elongation and meiotic recombination, in addition to the MBX, its C-terminal adjacent 104, and its N-terminal adjacent 49-, amino-acid domain are needed, respectively.
I.We found a new checkpoint pathway, Te11-Mre11, that is specific to DNA double-strand breakage (DSB), In mitotic cells, Rad53 and Rad9 and in meiotic cells, Mre4/Mek1, are required, respectively. The MRX plays a sensor against the DSB, activates the pathway, and proceeds recombination under the guidance of the activated pathway.
II.It is a new finding that not only rad51but also rad52 are necessary for DNA homology search. Rad51-Rad52-single-stranded DNA is the complex to do it. Rad52 is also required at the latest stage of recombination, production of a final recombinant molecule.
III.A new helicase gene MER3 was found which is specific to meiotic recombination. As a frequency of meiotic crossover specifically decreases in this mutant, determination of recombinant type, crossover type or gene conversion type, is probably carried out during a process of formation of recombination intermediate, not at the resolution stage of the recombination intermediate as assumed.

Report

(6 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (62 results)

All Other

All Publications (62 results)

  • [Publications] M.Shinohara, Sakai, K., Shinohara, A., Bishop, D.K.: "Crossover interference in Saccharomyces cerevisiae requires a TID1/RDH54- and DMC1-dependent pathway."Genetics. 163. 1273-1286 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Shinohara, Sakai, K., Ogawa, T., Shinohara, A.: "The N-terminal DNA binding domain of Rad52 promotes RAD51-independent recombination in Saccharomyces cerevisiae."Genetics. 164. 855-865 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsukamoto, M, Yamashita, K., Miyazaki, M., Shinohara, M., Shinohara, A.: "The N-terminal DNA binding domain of Rad52 promotes RAD51-independent recombination in Saccharomyces cerevisiae."Genetics. 165. 1703-1715 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki T., Bressan, D.A., Shinohara, M., Haber, J.E., A.Shinohara.: "In vivo assembly and disassembly of Rad51 and Rad52 complexes during double-strand break repair."EMBO. J.23.. 939-949 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zierhut, C., Berlinger, M., Rupp, C.Shinohara, A., F.Klein.: "Mnd1 is required for meiotic inter-homolog repair."Current Biology. 14(in press). 752-762 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Bishop, D.K., Y.Nikoiski, J.Oshiro, J.Chon, M.Shinohara, X.Chen: "High copy number suppression of the meiotic arrest caused by a dmc1 mutation : REC114 imposes an early recombination block and RAD54 promotes a DMC1-independent DSB repair pathway."Genes Cells. 4. 425-444 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morrison, C., A.Shinohara, E.Sonoda, Y.Yamaguchi-Iwai, M.Takata, R.R.Weichselbaum, S.Takeda: "The essential functions of human Rad51 are independent of ATP hydrolysis."Mol Cell Biol. 19. 6891-6897 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakagawa, T., H.Ogawa: "The Saceharomyces cerevisiae MER3 gene, encoding a novel helicase-like protein, is required for crossover control in meiosis."EMBO J. 18. 5714-5723 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morrison, C., E.Sonoda, N.Takao, A.Shinohara, K.Yamamoto, S.Takeda: "The controlling role of ATM in homologous recombinational repair of DNA damage."Embo J. 19. 463-471 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinohara, M., S.L.Gasior, D.K.Bishop, A.Shinohara: "Tid1/Rdh54 promotes colocalization of Rad51 and Dmc1 during meiotic recombination."Proc Natl Acad Sci USA. 97. 10814-10819 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takao, N., R.Mori, H.Kato, A.Shinohara, K.Yamamoto: "c-Abl tyrosine kinase is not essential for ataxia telangiectasia mutated functions in chromosomal maintenance."J Biol Chem. 275. 725-728 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tashiro, S., J.Walter, A.Shinohara, N.Kamada, T.Cremer: "Rad51 accumulation at sites of DNA damage and in postreplicative chromatin"J Cell Biol. 150. 283-291 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsubouchi, H., H.Ogawa: "Exol roles for repair of DNA double-strand breaks and meiotic crossing over in Saccharomyces cerevisiae."Mol Biol Cell. 11. 2221-2233 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Bakhlanova, I.V., T.Ogawa, V.A.Lanzov: "Recombinogenic activity of chimeric recA genes (Pseudomonas aeruginosa/ Escherichia coli) : a search for RecA protein regions responsible for this activity."Genetics. 159. 7-15 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hong, E.L., A.Shinohara, D.K.Bishop: "Saccharomyces cerevisiae Dmc1 protein promotes renaturation of single-strand DNA (ssDNA) and assimilation of ssDNA into homologous super-coiled duplex DNA."J Biol Chem. 276. 41906-41912 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kim, J.M., F.Maraboeuf, S.K.Kim, A.Shinohara, M.Takahashi: "Effect of ions and nucleotides on the interactions of yeast Rad51 protein with single-stranded oligonucleotides."J Biochem(Tokyo). 129. 469-475 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsukamoto, Y., A.K.Taggart, V.A.Zakian: "The role of the Mre11-Rad50-Xrs2 complex in telomerase-mediated lengthening of Saccharomyces cerevisiae telomeres."Curr Biol. 11. 1328-1335 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Usui, T., H.Ogawa, J.H.Petrini: "A DNA damage response pathway controlled by Tell and the Mre11 complex."Mol Cell. 7. 1255-1266 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yu, X., S.A.Jacobs, S.C.West, T.Ogawa, E.H.Egelman: "Domain structure and dynamics in the helical filaments formed by RecA and Rad51 on DNA."Proc Natl Acad Sci USA. 98. 8419-8424 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinohara, M., K.Sakai, A.Shinohara, D.K.Bishop: "Crossover interference in Saccharomyces cerevisiae requires a TID1/RDH54-and DMC1-dependent pathway."Genetics. 163. 1273-1286 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinohara, M., K.Sakai, T.Ogawa, A.Shinohara: "The mitotic DNA damage checkpoint proteins Rad17 and Rad24 are required for repair of double-strand breaks during meiosis in yeast."Genetics. 164. 855-865 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsukamoto, M., K.Yamashita, T.Miyazaki, M.Shinohara, A.Shinohara: "The N-terminal DNA-binding domain of Rad52 promotes RAD51-independent recombination in Saccharomyces cerevisiae."Genetics. 165. 1703-1715 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki, T., D.A.Bressan, M.Shinohara, J.E.Haber, A.Shinohara: "In vivo assembly and disassembly of Rad51 and Rad52 complexes during double-strand break repair."Embo J. 23. 939-949 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zierhut, C., M.Berlinger, C.Rupp, A.Shinohara, F.Klein: "Mnd1 is required for meiotic interhomolog repair."Curr Biol. 14. 752-762 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] M.Shinohara, Sakai, K., Shinohara, A., Bishop, D.K.: "Crossover interference in Saccharomyces cerevisiae requires a TID1/RDH54-and DMC1-dependent pathway."Genetics. 163. 1273-1286 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Shinohara, Sakai, K., Ogawa, T., Shinohara, A.: "The N-terminal DNA binding domain of Rad52 promotes RAD51-independent recombination in Saccharomyces cerevisiae."Genetics. 164. 855-865 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsukamoto, M., Yamashita, K., Miyazaki, M., Shinohara, M., Shinohara, A.: "The N-terminal DNA binding domain of Rad52 promotes RAD51-independent recombination in Saccharomyces cerevisiae."Genetics. 165. 1703-1715 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyazaki T., Bressan, D.A., Shinohara, M., Haber, J.E., A.Shinohara.: "In vivo assembly and disassembly of Rad51 and Rad52 complexes during double-strand break repair."EMBO. J.23.. 939-949 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Zierhut, C., Berlinger, M., Rupp, C., Shinohara, A., F.Klein.: "Mnd1 is required for meiotic inter-homolog repair."Current Biology. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 篠原 彰, 篠原 美紀: "染色体上でのDNA鎖交換反応-相同組換えの分子メカニズムと細胞機能"細胞工学. 278-282 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Usui, H.Ogawa, J.Petrini: "A DNA damage response pathway controlled by Tel1 and the Mre11 complex"Molecular Cell. 7. 1256-1266 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] X.Yu, S.A.Jacobs, S.C.West, T.Ogawa, E.H.Egelman: "Domain Structure and dynamics in the helical filaments formed by RecA and Rad51 on DNA"Proc.Natl.Acard.Sci.USA. 98. 8419-8424 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Tsukamoto, A.A.K.Taggart, V.A.Zakian: "The role of the Mre11-Rad50-Xrs2 complex in telomerase-mediated lengthening of Saccharomyces cerevisiae telomeres"Curr.Biol.. 11. 1328-1335 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] I.V.Bakhlanova, T.Ogawa, A.L.Lanzov: "Recombinogenic activity of chimeric recA genes (P.aeruginosa/E.coli). A search for RecA protein regions responsible for this activity"Genetics. 159. 7-15 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kim, J.-M., Maraboeul, F., Kim, S.K., Shinohara, A., M.Takahashi: "Effect of ions and nucleotides on the interaction of yeast Rad51 and E.coli RecA proteins with single-stranded oligonucleotides"J.Biochem. 129. 469-475 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hong, E.L., Shinohara, A., D.K.Bishop: "S.cerevisiae Dmc1 protein promotes renaturation of ssDNA and assimilation of ssDNA into homologous super-coiled duplex DNA"J.Biol.Chem.. 276. 41906-41912 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Shinohara, K.Sakai, A.Shinohara, D.K.Bishop: "Crossover interference in Saccharomyces cerevisiae requires a TID1/RDH54 and DMC1-dependent pathway"Genetics. 163(印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Shinohara, K.Sakai, T.Ogawa, A.Shinohara: "The mitotic DNA damage checkpoint proteins Rad17 and rad24 are required for repair of double-strand breaks during meiosis in yeast"Genetics. 163(印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 篠原 彰, 篠原 美紀: "染色体上でのDNA鎖交換反応-相同組換えの分子メカニズムと細胞機能"細胞工学. 22. 278-282 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 小川智子: "DNA研究に明け暮れた私の40年"蛋白質・核酸・酵素. 48巻5号. 681-683 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 小川英行: "DNAのしっぽ"蛋白質・核酸・酵素. 48巻5号. 678-680 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 小川 英行: "ゲノムの修復と組換え"シュプリンガー・フェアラーク東京. 161 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 小川 智子: "分子生物学イラストレイテッド"羊土社. 380 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Usui, H.Ogawa, J.Petrini: "A DNA damage response pathway controlled by Tel1 and the Mre11 complex"Molecular Cell. 7. 1256-1266 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] X.Yu, S.A.Jacobs, S.C.West, T.Ogawa, E.H.Egelman: "Domain Structure and dynamics in the helical filaments formed by RecA and Rad5 on DNA"Proc. Natl. Acard. Sci. USA. 98. 8419-8424 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Tsukamoto, A.A.K.Taggart, V.A.Zakian: "The role of the Mre11-Rad50--Xrs2 complex in telonmerase-mediated lengthening of Saccharomyces cerevisiae telomeres"Curr. Biol.. 11. 1328-1335 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] I.V.Bakhlanova, T.Ogawa, A.L.Lanzov: "Recombinogenic activity of chimeric recA genes (P. aeruginosa/E. coli ). A search for RecA protein regions responsible for this activity"Genetics. 159. 7-15 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kim, J.M., Maraboeul, F., Kim, S.K., Shinohara, A., M.Takahashi: "Effect of ions and nucleotides on the interaction of yeast Rad51 and E. coli RecA proteins with single-stranded oligonucleotides"J. Biochem. 129. 469-475 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hong, E.L., Shinohara, A., D.K.Bishop: "S. cerevisiae Dmc1 protein promotes renaturation of ssDNA and assimilation of ssDNA into homologous super-coiled duplex DNA"J. Biol. Chem.. 276. 41906-41912 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Xiong Yu,Steven: "Domain Structure and Dynamics in the Helical Filaments Formated by RecA and Rad51 on DNA"Proc.Natl.Acadm.Scl. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsutomu,Ohta: "Recognition of G-structure at Telomere Ends and its Dissolution by Yeast Mre11"Nature Genetics. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 臼井雄彦: "DNA2重鎖切断を伴う多様な生理機構におけるMre11/Rad50/Xrs2蛋白質複合体の役割"核酸 蛋白質 酵素(共立出版)(印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 押海裕之: "出芽酵母Mre11単蛋白質の遺伝的組換えとDNA傷害の修復過程における機能"核酸 蛋白質 酵素(共立出版). 631-635 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小川智子: "個性を生み出す遺伝的組換えの仕組み"生殖細胞1-その誕生と振る舞い「大学と科学」公開シンポジウム クバプロ. 85-97 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hideo Tsubouchi: "Exol roles for repair of DNA double-strand breaks and meiotic crossing over in Saccharomyces cerevisiae"Mol. Blol. Cell. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Arika Shinohara: "Rad51/RecA protein families and the associated proteins in eukaryotes"Mutatlon Res. 435. 13-21 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takuro Nakagawa: "The Saccharomyces cerevisiae MER3 gene, encoding a novel helicase-like protein, is required for crossover control in meiosis"EMBO J.. 18. 5714-5723 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takehiko Usui: "Complex formation and functional versatility of Mrell of budding yeast in recombination"Cell. 95. 705-716 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akira Shinohara: "Stimulation of Rad51-mediated Recombination by Rad52 in Saccharomyces cerevisiae"Nature. 391. 404-407 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akira Shinohara: "Rad51-independet Homologous Recombination Mediated by Rad52"Genes to Cells. 3. 145-156 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 押海裕之: "組換えに関与するMrell機能の多様性の出現のしくみ"実験医学「トピックス」(羊土社). 757-760 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 太田力: "真核生物の組換え反応の多様性"核酸 蛋白質 酵素 (共立出版). 1830-1837 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2018-03-28  

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