細胞複製制御の分子生物学的研究

• 研究課題/領域番号: 04256101
• 研究種目: 重点領域研究
• 配分区分: 補助金
• 研究機関: 名古屋大学
• 研究代表者: 岡崎 恒子 名古屋大学, 理学部, 教授 (10022584)
• 研究分担者: 山本 正幸 東京大学, 大学院・理学系研究科, 教授 (40114706) ; 花岡 文雄 大阪大学, 細胞生体工学センター, 教授 (50012670) ; 平賀 壮太 熊本大学, 医学部, 教授 (40027321) ; 吉川 寛 奈良先端科学技術大学院大学, バイオサイエンス研究科, 教授 (70019876)
• 研究期間 (年度): 1995
• 研究課題ステータス: 完了 (1995年度)
• 配分額: 73,500千円 (直接経費: 73,500千円); 1995年度: 3,000千円 (直接経費: 3,000千円); 1994年度: 13,900千円 (直接経費: 13,900千円); 1993年度: 26,600千円 (直接経費: 26,600千円); 1992年度: 30,000千円 (直接経費: 30,000千円)
• キーワード: ゲノム複製 / 複製起点 / 開始蛋白 / ゲノム分配 / 複製終結 / セントロメア / ゲノム複製の開始 / ゲノム複製の終結 / ゲノムの分配 / 細胞周期 / 増殖制御とがん化 / 増殖制御と分化 / 増殖制御の情報伝達 / 複製酵素

研究概要

本重点領域研究では、原核生物並びに真核生物の細胞複製における調節(制御)の仕組みを、分子レベルで総合的に理解することを目的として平成3年度から4年間行われた。総括斑は「ゲノム複製の開始の制御」(課題1)、「ゲノム複製終結と分配の制御」(課題2)、「細胞複製制御の遺伝子発現」(課題3)の3課題について計画研究斑を組織し重点的に研究を推進するとともに、萌芽的公募研究を加えて、総合的な視点から研究を推進した。本年度は平成3年度〜6年度の間に本重点領域で行なわれた研究成果のとりまとめと評価を行ない更に今後の研究を展望するために以下の活動を行った。
1.研究課題ごとの成果とりまとめと評価
総括班幹事(領域代表、研究班代表、サ-キュラー担当者)が中心となり、班員により行なわれた研究の成果と目標達成度を評価し、今後の本課題分野の進展方向も含めたとりまとめと総括を行なった。
2.公開ワークショップ
平成7年8月29日〜31日、大阪府四条畷市アイアイランドにおいて、本重点領域ならびに一般の研究者の参加を得て公開ワークショップを行ない、研究成果の発表・討論、今後の方向などについて討論した。これにより班員の研究成果の公開と、広い層の研究者や総括班評価委員による評価を得た。
3.研究成果報告書の作成
平成7年10月に研究分担者全員より本重点領域で行なわれた研究成果の要旨と発表論文リスト並びに領域代表者及び計画研究班代表による研究の総括を加えた研究成果報告書(冊子)を作成した。この冊子は全班員並びに関連分野研究者に配布した。
研究費はこれらの活動のための旅費、会議費、報告書印刷費、発送代等にあてた。

研究成果

• [文献書誌] M.Suzuki: "Prediction of the three dimentional structure of the DBD of centromere protein B (CENP-B) in comparison with the structures of Myb,LexA and DtxR DBDs." Proc.Japan Acad.71,B. 153-157 (1995)
• [文献書誌] C.Obuse: "A replication-enhancing element with transcriptional Silencer activity in autonomously replicating human chromosomal fragments." Mol.Biol.Cell. 7. 43-55 (1996)
• [文献書誌] R.Kitagawa: "A novel DnaA protein-binding site at 94.7min of the Escherichia coli chromosome." Mol.Microbiol.in press.
• [文献書誌] K.Yamanaka: "Characterization of the smtA gene encoding an S-adenosylmethionine-dependent methyltransferase of Escherichia coli." FEMS Microbiol.Letters. 133. 59-63 (1995)
• [文献書誌] K.Yamanaka: "Identification of two new genes,mukE and mukF,involved in chromosome partitioning in Escherichia coli." Mol.Gen.Genet.250(in press). (1996)
• [文献書誌] Y.Iino: "The role of cdc2 and other genes in meiosis in Schizosaccharomyces pombe." Genetics. 140. 1235-1245 (1995)
• [文献書誌] H.Izumiya: "Cloning and functional analysis of the ndkl gene encoding nucleoside diphosphate kinase in Schizosaccharomyces pombe." J.Biol.Chem.17. 27859-27864 (1995)
• [文献書誌] J.Kanoh: "Schizosaccharomyces pombe zfsl+encoding a zinc-finger protein functions in the mating pheromone recognition pathway." Mol.Biol.Cell. 6. 1185-1195 (1995)
• [文献書誌] M.Yamamoto: "The molecular control mechanisms of meiosis in fission yeast." Trends Biochem.Sci.21. 18-22 (1996)
• [文献書誌] T.Ogawa: "Cell cycle-dependent transcription from the gid and mioC promoters of Escherich coli." J.Bact.176. 1609-1615 (1994)
• [文献書誌] M.Ikeno: "Distribution of CENP-B boxes reflected in CREST centromere antigenic sites on long-range α-site DNA arrays of human chromosome 21." Human Mol.Genet.3. 1245-1257 (1994)
• [文献書誌] N.Seki: "Mapping of the human centromere protein B gene (CENPB) to chromosome 20p13 by fluorescence in situ hybridization." Genomics. 24. 187-188 (1994)
• [文献書誌] K.Kitagawa: "Analysis of protein-DNA and protein-protein interactions of centromere protein B (CENP-B) and properties of the complex in the cell cycle." Mol.Cell.Biol.in press (1995)
• [文献書誌] M.Yamazoe: "A protein which binds preferentially to single-stranded core sequence of autonomously replicating sequence is essential for respiratory function in mitochondria of Saccharomyces cerevisiae." J.Biol.Chem.269. 15244-15252 (1994)
• [文献書誌] M.B.Rashid: "Anatomy of the stimulative sequences flanking the ARS consensus sequence of chromosome VI in saccharomyces cerevisiae." Gene. 150. 213-220 (1994)
• [文献書誌] K.Yamanaka: "Cloning,sequencing,and characterization of multicopy suppressors of mukB mutation in Escherichia coli." Mol.Microbiol.13. 301-312 (1994)
• [文献書誌] K.Yamanaka: "Two mutant alleles of mukB,a gene essential for chromosome partition in Escherichia coli." FEMS Microbiol.Lett.123. 27-32 (1994)
• [文献書誌] K.Yamanaka: "Characterization of translucent segments obserbed in an smbA mutant of Escherichia coli." FEMS Microbiol.Lett.116. 61-66 (1994)
• [文献書誌] K.Yamanaka: "Multicopy suppressors,mssA and mssB,of an smbA mutation of Escherichia coli." Mol.Gen.Genet.243. 9-16 (1994)
• [文献書誌] W.Pendergrass: "A murine temperature-sensitive DNA polymerase α mutant displays a diminished capacity to stimulate DNA synthesis in senescent human fibroblast nuclei in heterokaryons at the non-permissive condition." J.Cell.Physiol.158. 270-276 (1994)
• [文献書誌] M.Izumi: "Identification of a point mutation in the cDNA of the catalytic subunit of DNA polymerase α from a temperature-sensitive mouse FM3A cell line." J.Biol.Chem.269. 7639-7644 (1994)
• [文献書誌] C.Masutani: "Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23." EMBOJ.13. 1831-1843 (1994)
• [文献書誌] T.Icho: "A novel human gene that is preferentially transcribed in heart muscle." Gene. 144. 301-306 (1994)
• [文献書誌] M.Tanaka: "Roles of endogenous nitric oxide in the cerebellar cortical development slice culture." Neuroreport. 5. 2049-2052 (1994)
• [文献書誌] P.J.van der Spek: "Chromosomal localization of three repair genes:the xeroderma pigmentosum group C gene and two homologs of yeast RAD23." Genemics. 23. 651-658 (1994)
• [文献書誌] M.Seki: "Moleacular cloning of cDNA encoding human DNA helicace Q1 which has homology to Escherichia coli RecQ helicase and localization of the gene at chromosome 12p12." Nucl.Acids Res.22. 4566-4573 (1994)
• [文献書誌] T.Matsuda: "DNA repair protein XPA binds replication protein A(RPA)." J.Biol.Chem.(in press). (1995)
• [文献書誌] Y.Tsutsumi-Ishii: "Response of heat shock element (HSE) within the human HSP70 promoter to mutated p53 genes." Cell Growth Differ.(in press). (1995)
• [文献書誌] Y.watanabe: "S.pombe mei2^+ encodes an RNA-binding protein essential for premeiotic DNA synthesis and meiosis." Cell. 78. 487-498 (1994)
• [文献書誌] M.Nocero: "Glucose repression of fbp1 transcription in Schizosaccahromyces pombe is partially regulated by adenylate cyclase activation by a G protein α subunity encoded by gpa2(git8)." Genetics. 138. 39-45 (1994)
• [文献書誌] D.A.Hughes: "Transcriptional regulation of a Ras nucleotide-exchange factor gene by extracellular signals in fission yeast." J.Cell Sci.107. 3635-3642 (1994)
• [文献書誌] T.Kuromori: "Cloning of cDNAs from Arabidopsis thaliana that encode putative protein phosphatase 2C and human Dr1-like protein by transformation of a fission yeast mutant." Nucl.Acids Res.22. 5296-5301 (1994)
• [文献書誌] J.Davey: "Isolation and characterization of Krp,a dibasic endopeptidase required for cell viability in the fission yeast Schizosaccharomyces pombe." EMBOJ.13. 5910-5921 (1994)
• [文献書誌] A.Pichova: "New Arrays of cytoplasmic microtubules in the fission yeast Schizosaccharomyces pombe." Protoplasma. (in press). (1995)
• [文献書誌] H.Kunitomo: "Schizosaccharomyces pombe pac2^+ controls the onset of sexual development via a pathway independent of the cAMP cascade." Curr.Genet.(in press). (1995)
• [文献書誌] H.Masumoto: "Properties of CENP-B and its target sequence in satellite DNA." NATO ASI Series:Chromosome Segregation and Aneuploidy. H72. 31-43 (1993)
• [文献書誌] H.Masukata: "Autonomous replication of human chromosomal DNA fragments in human cells." Mol.Biol.Cell. 4. 1121-1132 (1993)
• [文献書誌] T.Ogawa: "Cell cycle-dependent transcription from the gid and mioC promoters of Escherichia coli." J.Bact.176(in press). (1994)
• [文献書誌] K.Shirahige: "Location and characterization of autonomously replicating sequences(ARSs)from chromosome VI of Saccharomyces cerevisiae." Mol.Cell.Biol.13. 5043-5056 (1993)
• [文献書誌] H.Yoshikawa: "Initiation and termination of chromosome replication." Bacillus subtilis and other Gram-positive bacteria:Biochemistry,Physiology and Molecular Genetics. 507-528 (1993)
• [文献書誌] M.Yamazoe: "A protein which binds preferentially to single-stranded core sequence of ARS is essential for respiratory function in mitochondria of Saccharomyces cerevisiae." J.Biol.Chem.(in press). (1994)
• [文献書誌] S.Hiraga: "E.coli chromosome partition." Current Opinion in Genetics & Development. 5. 789-801 (1993)
• [文献書誌] Y.Feng: "New killing system controlled by two genes located immediately upstream of the mukB gene in E.coli." Mol.Gen.Genet.(in press). (1993)
• [文献書誌] T.Tomoyasu: "The Escherichia coli FtsH protein is a prokaryotic member of a protein family of putative ATPases involved in membrane functions,cell cycle control and gene expression." J.Bacteriol.175. 1344-1351 (1993)
• [文献書誌] T.Tomoyasu: "Topology and subcellular localization of FtsH protein in Escherichia coli." J.Bacteriol. 175. 1352-1357 (1993)
• [文献書誌] C.Herman: "Cell growth and λ development controlled by the same essential Escherichia coli,ftsH/hflB." Proc.Natl.Acad.Sci.USA. 90. 10861-10865 (1993)
• [文献書誌] K.Yamanaka: "Multicopy suppressors,mssA and mssB,of an smbA mutation of Escherichia coli." Mol.Gen.Genet.(in press). (1994)
• [文献書誌] K.Yamanaka: "Characterization of translucent segments observed in an smbA mutant of Escherichia coli." FEMS Microbiol.Lett.(in press). (1994)
• [文献書誌] H.Miyazawa: "Molecular cloning of the cDNAs for the four subunits of mouse DNA polymerase α-primase complex and their gene expression during cell proliferation and the cell cycle." J.Biol.Chem.268. 8111-8122 (1993)
• [文献書誌] K.Matsumoto: "TAF-l,a novel host factor required to stimulate the adenovirus core DNA replication." J.Biol.Chem.268. 10582-10587 (1993)
• [文献書誌] W.R.Pendergrass: "A murine temperature-sensitive DNA polymerase a mutant displays a diminished capacity to stimulate DNA synthesis in senescent human fibroblast nuclei in heterokaryons at the nonpermissive condition." J.Cell.Physiol. (in press). (1994)
• [文献書誌] M.Izumi: "Identification of a point mutation in the cDNA of the catalytic subunit of DNA polymerase α from a temperature-sensitive mouse FM3A cell line." J.Biol.Chem.(in press). (1994)
• [文献書誌] K.Tanaka: "Schizosaccharomyces pombe map3^+ encodes the putative M-factor receptor." Mol.Cell.Biol.13. 80-88 (1993)
• [文献書誌] S.Tabata: "Evidence of meiosis-specific regulation of gene expression in lily microsporocytes." Plant Sci.89. 31-41 (1993)
• [文献書誌] Y.Gotoh: "Schizosaccharomyces pombe Spk1 is a tyrosine-phosphorylated protein functionally related to Xenopus mitogen-activated protein kinase." Mol.Cell.Biol.13. 6427-6434 (1993)
• [文献書誌] Y.Imai: "The fission yeast mating pheromone P-factor:Its molecular structure,gene structure,and ability to induce gene expression and G1 arrest in the mating partner." Genes & Dev.(in press). (1994)
• [文献書誌] T.Maeda: "Cloning of the pka1 gene encoding the catalytic subunit of the cAMP-dependent protein kinase in Schizosaccharomyces pombe." J.Biol.Chem.(in press). (1994)
• [文献書誌] Y.Muro: "Centromere protein B assembles human centromeric α-satellite DNA at the 17-bp sequence,CENP-B box." J.Cell Biol.116. 585-596 (1992)
• [文献書誌] K.Yoda: "A human centromere protein,CENP-B,has a DNA binding domain containing four potential α helices at the NH_2 terminus,which is separable from dimerizing activity." J.Cell Biol.119. 1413-1427 (1992)
• [文献書誌] K.Shirahige: "Location and characterization of autonomously replicating sequences (ARSs) from chromosome VI of Saccharomyces cerevisiae." Mol.Cell.Biol.
• [文献書誌] K.J.Begg: "Escherichia coli mutant Y16 is a double mutant carrying thermosensitive ftsH and ftsI mutants." J.Bacteriol.174. 2416-2417 (1992)
• [文献書誌] S.Hiraga: "Chromosome and plasmid partition in Escherichia coli." Ann.Rev.Biochem.61. 283-306 (1992)
• [文献書誌] R.Imamura: "Characterization of high molecular weights of complexes and polymers of cytoplasmid proteins in Escherichia coli." Res.Microbiol.143. 743-753 (1992)
• [文献書誌] K.Yamanaka: "Identification and characterization of the smbA gene,a suppressor of the muB null mutant of Escherichia coli." J.Bacteriol.174. 7517-7526 (1992)
• [文献書誌] H.Niki: "E.coli MukB protein involved in chromosome partition forms a homodimer with a rod-and-hinge structure having DNA binding and ATP/GTP binding activities." EMBO J.11. 5101-5109 (1992)
• [文献書誌] Y.Ishimi: "Topoisomerase II plays an essential role as a sivelase in the late stage of SV40 chromosome replication in vitro." J.Biol.Chem.267. 462-466 (1992)
• [文献書誌] K.Sugasawa: "Non-conservative segregation of parental nucleosomes during simian virus 40 chromosome replication in vitro." Proc.Natl.Acad.Sci.USA. 89. 1055-1059 (1992)
• [文献書誌] D.Ayusawa: "Complementation by a cloned human ubiquitin-activating enzyme El of the S-phase-arrested mouse FM3A cell mutant with thermolabile El." Cell Struct.Funct.17. 113-122 (1992)
• [文献書誌] K.Ozawa: "Mapping of the human GSPTl gene,a human homolog of the yeast GST1 gene,to chromosomal band 16p13.1." Somat.cell Mol.Genet.18. 189-194 (1992)
• [文献書誌] F.Yatagai: "Resolution and characterization of polymorphic DNA by SSCP and chemical cleavage methodologies." J.Rad.Res.33. 95-108 (1992)
• [文献書誌] T.H.Norwood: "A Somatic genetic approach to the analysis of senescence in human diploid fibroblast in vitro:from heterokaryons to molecules." Exp.Gerontol.27. 391-395 (1992)
• [文献書誌] H.Kamiya: "An abasic site analogue activates a c-Ha-ras gene by a point mutation at modified and adjacent positions." Nucleic Acids Res.20. 4409-4415 (1992)
• [文献書誌] T.Sudo: "The c-myb proto-oncogene product binds to bu does not activate the promoter of the DNA polymerase α gene." Oncogene. 7. 1999-2006 (1992)
• [文献書誌] N.Iwai: "Cloning and sequence of a functionally active cDNA for mouse ubiquitin-activating enzyme E." Gene. 118. 279-282 (1992)
• [文献書誌] K.Segawa: "Abrogation of p53-mediated transactivation by SV40 large T antigen." Oncogene.
• [文献書誌] H.Miyazawa: "Molecular cloning of the cDNAs for the four subunits of mouse DNA polymerase α-primase complex and their gene expression during cell proliferation and the cell cycle." J.Biol.Chem.268. (1993)
• [文献書誌] K.Sugasawa: "Cell-free repair of UV-damaged simian virus 40 chromosomes in human cell extracts.I.Develpment of a cellfree system detecting excision repair of UV-irradiated SV40 chromosomes." J.Biol.Chem.268. (1993)
• [文献書誌] C.Matsutani: "Cell-free repair of UV-damaged simian virus 40 chromosomes in human cell extracts.II.Defective DNA repair synthesis by xeroderma pigmentosum cell extracts." J.Biol.Chem.268. (1993)
• [文献書誌] K.Matsumoto: "TAF-I,a novel host factor required to stimulate the adenovirus core DNA replication." J.Biol.Chem.268. (1993)
• [文献書誌] Y.Imai: "S.pombe sxa1^+ and sxa2^+ encode putative proteases involved in the mating response." Mol.Cell.Biol.12. 1827-1834 (1992)
• [文献書誌] N.Mochizuki: "Reduction in the intracellular cAMP level triggers initiation of sexual development in fission yeast." Mol.Gen.Genet.233. 17-24 (1992)
• [文献書誌] T.Isshiki: "Characterization of a fission yeast gene,gpa2,that encode a G-alpha subunit involved in the monitoring of nutrition." Genes and Dev.6. 2455-2462 (1992)
• [文献書誌] K.Tanaka: "Schizosaccharomyces pombe map3^+ encodes the putative Mfactor receptor." Mol.Cell.Biol.13. 80-88 (1993)