DNA修復機構の、逆遺伝学的手法(ニワトリ細胞株とメダカ)による機能解析

2009 年度 研究成果報告書

• 研究課題/領域番号: 17013039
• 研究種目: 特定領域研究
• 配分区分: 補助金
• 審査区分: 生物系
• 研究機関: 京都大学
• 研究代表者: 武田 俊一 京都大学, 大学院・医学研究科, 教授 (60188191)
• 研究分担者: 谷口 善仁 京都大学, 大学院・医学研究科, 准教授 (00324616)
• 研究期間 (年度): 2005 – 2009
• キーワード: 癌 / ゲノム / 細胞・組織 / バイオテクノロジー / 放射線

研究概要

抗がん治療は、放射線のように,染色体DNA を損傷し、細胞自殺を誘導するものが多い。この理由から、各修復因子の機能を解析することは、抗がん治療の効果を増大させることに役立つ。機能解析には、逆遺伝学的解析が有効である。我々は、ニワトリDT40細胞とメダカというユニークな逆遺伝学的実験手法を開発した。DT40の解析から、我々は、ユビキチン化、DNAポリメラーゼ、BRCA1/2の機能解析に貢献した。

研究成果

• [雑誌論文] accumulation of RAD51 at double-strand (2010) GEMIN2 promotes breaks in homologous recombination. (2010)
  • 著者名/発表者名: Takizawa Y, Qing Y, Takaku M, Ishida T, Morozumi Y, Tsujita T, Kogame T, Hirota K, Takahashi M, Shibata T, Kurumizaka H, Takeda S.
  • 雑誌名: Nucleic Acids Res. (in press)
  • 査読あり
• [雑誌論文] DNA polymerasesνandθare Takeda S. required for efficient Immunoglobulin V gene diversification in chicken. (2010)
  • 著者名/発表者名: Kohzaki M, Nishihara K, Hirota K, Sonoda E, Yoshimura M, Ekino S, Butler JE, Watanabe M, Halazonetis T
  • 雑誌名: J C e l l B i o l. (in press)
  • 査読あり
• [雑誌論文] Collaborative action of Brca1 Taniguchi and CtIP in elimination of covalent modifications from double-strand breaks to facilitate subsequent break repair. (2010)
  • 著者名/発表者名: Nakamura K, Kogame T, Oshiumi H, Shinohara A, Sumitomo Y, Agama K, Pommier Y, Tsutsui KM, Tsutsui K, Hartsuiker E, Ogi T, Takeda S, Y.
  • 雑誌名: P L o S G e n e t. 6 ページ: e1000828
  • 査読あり
• [雑誌論文] PTIP promotes DNA double-strand break repair through homologous recombination. (2010)
  • 著者名/発表者名: Wang X, Takenaka K, Takeda S.
  • 雑誌名: G e n e s C e l l s (in press)
  • 査読あり
• [雑誌論文] approach using DNA-repair-deficient (2010) A novel chicken DT40 cell lines for screening and characterizing the genotoxicity of environmental contaminants. (2010)
  • 著者名/発表者名: Ji K, Kogame T, Choi K, Wang X, Lee J, Taniguchi Y, Takeda S.
  • 雑誌名: Environ Health Perspect. 117 ページ: 1737-44
  • 査読あり
• [雑誌論文] Bloom DNA helicase facilitates Hirota K. (2009) homologous recombination between diverged homologous sequences. (2009)
  • 著者名/発表者名: Kikuchi K, Abdel-Aziz HI, Yamazoe M, Taniguchi Y, Takeda S
  • 雑誌名: J B i o l C h e m. 284 ページ: 26360-7
  • 査読あり
• [雑誌論文] the non-homologous end-joining repair Okada N. (2009) Genetic evidence that pathway is involved in LINE retrotransposition. (2009)
  • 著者名/発表者名: Suzuki J, Yamaguchi K, Kajikawa M, Ichiyanagi K, Adachi N, Koyama H, Takeda S
  • 雑誌名: P L o S G e n e t. 5 ページ: e1000461
  • 査読あり
• [雑誌論文] An ATM and ATR Takeda S, dependent checkpoint inactivates spindle assembly by targeting CEP63. (2009)
  • 著者名/発表者名: Smith E, Dejsuphong D, Balestrini A, Hampel M, Lenz C, Vindigni A, Costanzo V.
  • 雑誌名: N a t C e l l B i o l. 11 ページ: 278-85
  • 査読あり
• [雑誌論文] for single-strand lesions initiating (2009) Genetic evidence Nbs1-dependent homologous recombination in diversification of Ig V in chicken B lymphocytes. (2009)
  • 著者名/発表者名: Nakahara M, Sonoda E, Nojima K, Sale JE, Takenaka K, Kikuchi K, Nakamura K, Sumitomo Y, Bree RT, Lowndes Taniguchi Y, NF, Takeda S.
  • 雑誌名: P L o S G e n e t. 5 ページ: e1000356
  • 査読あり
• [雑誌論文] Cohesin associates with Fukagawa T, Yen TJ, Yokomori spindle poles in a mitosis-specific manner and functions in spindle assembly in vertebrate cells. (2009)
  • 著者名/発表者名: Kong X, Ball AR, Jr., Sonoda E, Feng J, Takeda S, K.
  • 雑誌名: M o l B i o l C e l l. 20 ページ: 1289-301
• [雑誌論文] Cyclin-dependent kinases and cell-cycle Hunt T. transitions: does one fit all? (2008)
  • 著者名/発表者名: Hochegger H, Takeda S
  • 雑誌名: Nat Rev M o l C e l l B i o l 9(Review) ページ: 910-6
  • 査読あり
• [雑誌論文] PARP-1 ensures the modulation of replication Okumura K. fork progression by homologous recombination on damaged DNA. (2008)
  • 著者名/発表者名: Sugimura K, Takebayashi S, Taguchi H, Takeda S
  • 雑誌名: J C e l l B i o l. 183 ページ: 1203-12
  • 査読あり
• [雑誌論文] The 9-1-1 DNA clamp is Takeda S, required for immunoglobulin gene conversion. (2008)
  • 著者名/発表者名: Saberi A, Nakahara M, Sale JE, Kikuchi K, Arakawa H, Buerstedde J-M, Sonoda E.
  • 雑誌名: M o l C e l l B i o l. 28 ページ: 6113-22
  • 査読あり
• [雑誌論文] Single stranded DNA binding protein hSSB1 is critical for genomic stability. (2008)
  • 著者名/発表者名: Richard D, Bolderson E, Cubeddu L, Wadsworth RIM, Savage K, Sharma GG, Nicolette ML, Tsvetanov S, McIlwraith MJ, Pandita R, Takeda S, West SC, Paull TT, Pandita1 TK, White MF, Hay TT, Gautier J, Khanna KK.
  • 雑誌名: N a t u r e 453 ページ: 677-81
  • 査読あり
• [雑誌論文] DNA damage response protein ASCIZ links base excision repair with immunoglobulin gene conversion. (2008)
  • 著者名/発表者名: Oka H, Sakai W, Sonoda E, Nakamura J, Asagoshi K, Wilson SH, Kobayashi M, Yamamoto K, Heierhorst J, Takeda S, Taniguchi Y.
  • 雑誌名: B i o c h e m B i o p h y s R e s C o m m u n. 371 ページ: 225-9
  • 査読あり
• [雑誌論文] Ctp1/CtIP and the MRN Taniguchi Y, complex collaborate in the initial steps of homologous recombination. (2007)
  • 著者名/発表者名: Takeda S, Nakamura K, Paull TT.
  • 雑誌名: M o l C e l l. 28(Review) ページ: 351-2
  • 査読あり
• [雑誌論文] Connecting the Dots between Septins and the DNA Damage Checkpoint. (2007)
  • 著者名/発表者名: Kinoshita M, Takeda S.
  • 雑誌名: C e l l 130(Review) ページ: 777-9
  • 査読あり
• [雑誌論文] RAD51 up-regulation bypasses BRCA1 function Bishop DK. and is a common feature of BRCA1-deficient breast tumors. (2007)
  • 著者名/発表者名: Martin RW, Orelli BJ, Yamazoe M, Minn AJ, Takeda S
  • 雑誌名: C a n c e r R e s. 67 ページ: 9658-65
  • 査読あり
• [雑誌論文] Functional interactions between BLM and XRCC3 in the cell. (2007)
  • 著者名/発表者名: 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.
  • 雑誌名: J C e l l B i o l. 179 ページ: 53-63
• [雑誌論文] Inhibitors of the proteasome suppress homologous DNA recombination in mammalian cells. (2007)
  • 著者名/発表者名: Murakawa Y, Sonoda E, Barber LJ, Zeng W, Yokomori K, Kimura H, Niimi A, Lehmann AR, Zhao GY, Hochegger H, Boulton SJ, Takeda S.
  • 雑誌名: C a n c e r R e s. 67 ページ: 8536-8543
  • 査読あり
• [雑誌論文] An essential role for Cdk1 in S phase control, revealed by chemical genetics in vertebrate cells. (2007)
  • 著者名/発表者名: Hochegger H, Dejsuphong D, Sonoda E, Saberi A, Rajendra E, Kirk J, Hunt T, Takeda S.
  • 雑誌名: J C e l l B i o l. 178 ページ: 257-68
  • 査読あり
• [雑誌論文] Poly (ADP-ribose) Takeda S, Polymerase-1 Accelerates Single-Strand Break Repair in Concert with Poly (ADP-ribose) Glycohydrolase. (2007)
  • 著者名/発表者名: Fisher A, Hochegger H, Caldecott KW.
  • 雑誌名: M o l C e l l B i o l. 27 ページ: 5597-5605
  • 査読あり
• [雑誌論文] RAD18and poly[ADPribose]polymerase independently suppress the access of nonhomologous end joining to double strand breaks and facilitate homologous recombination mediated repair. (2007)
  • 著者名/発表者名: Saberi A, Hochegger H, Szuts D, Lan L, Yasui A, Sale JE, Taniguchi Y, Y, Hua W, Yokomori K, Helleday T, Teraoka Murakawa H, Arakawa H, Buerstedde JM, Takeda S.
  • 雑誌名: M o l C e l l B i o l. 27 ページ: 2562-2571
  • 査読あり
• [雑誌論文] Cooperative Roles of Vertebrate Fbh1 and Blm DNA Helicases in Avoidance of Crossovers during Recombination Initiated by Replication Fork Collapse. (2007)
  • 著者名/発表者名: Kohzaki M, Hatanaka A, Sonoda E, Yamazoe M, Kikuchi K, Trung NV, Szuts D, Sale JE, Shinagawa H, Watanabe M, Takeda S.
  • 雑誌名: M o l C e l l B i o l. 27 ページ: 2812-2820
  • 査読あり
• [雑誌論文] A critical role for the ubiquitin-conjugating enzyme Ubc13 in initiating homologous recombination. (2007)
  • 著者名/発表者名: Zhao GY, Sonoda E, Barber LJ, Oka H, Murakawa Y, Yamada K, Ikura T, Wang X, Kobayashi M, Yamamoto K, Boulton SJ, Takeda S.
  • 雑誌名: M o l C e l l. 25 ページ: 663-675
  • 査読あり
• [雑誌論文] Generation of medaka gene knockout models by target-selected mutagenesis. (2006)
  • 著者名/発表者名: Taniguchi Y, Takeda S, M, Kamei Y, Todo T, Sasado T, Deguchi T, Furutani-Seiki Kondoh H, Mudde J, Yamazoe M, Hidaka M, Mitani H, Toyoda A, Sakaki Y, Plasterk RH, Cuppen E.
  • 雑誌名: G e n o m e B i o l. 7(12) ページ: R116
  • 査読あり
• [雑誌論文] Vertebrate POLQ and POL cooperate in Base Excision Repair ofβOxidative DNA Damage. (2006)
  • 著者名/発表者名: Yoshimura A, Kohzaki M, Nakamura J, Asagoshi K, Sonoda E, Hou E, Prasad R, Wilson SH, Tano K, Yasui A, Lan L, Seki M, Wood RD, Arakawa H, Buerstedde JM, Hochegger H, Okada T, Hiraoka M, Takeda S.
  • 雑誌名: M o l C e l l. 24 ページ: 115-25
  • 査読あり
• [雑誌論文] Ubiquitin-Binding Motifs in REV1 Protein Are Required For Its Role in the Tolerance of DNA Damage. (2006)
  • 著者名/発表者名: Guo C, Tang TS, Bienko M, Parker JL, Bielen AB, Sonoda E, Takeda S, Dikic I, Ulrich HD, Friedberg EC.
  • 雑誌名: M o l C e l l B i o l. 26 ページ: 8892-900
  • 査読あり
• [雑誌論文] end-joining and homologous Differential usage of non-homologous recombination in double strand break repair. (2006)
  • 著者名/発表者名: Sonoda E, Hochegger H, Saberi A, Taniguchi Y, Takeda S.
  • 雑誌名: D N A R e p a i r ( A m s t ) 5(Review) ページ: 1021-9
  • 査読あり
• [雑誌論文] Interacts with PCNA: Significance of the REV1 BRCT Domain In Vitro and In REV1 Protein Vivo. (2006)
  • 著者名/発表者名: Guo C, Sonoda E, Tang TS, Parker JL, Bielen AB, Takeda S, Ulrich HD, Friedberg EC.
  • 雑誌名: M o l C e l l. 23 ページ: 265-71
  • 査読あり
• [雑誌論文] Genetic dissection of vertebrate 53BP1: a major role in non-homologous end joining of DNA double strand breaks. (2006)
  • 著者名/発表者名: akamura K, Sakai W, Kawamoto T, Bree RT, Lowndes NF, Takeda S, Taniguchi Y.
  • 雑誌名: D N A R e p a i r ( A m s t ) 5 ページ: 741-749
  • 査読あり
• [雑誌論文] Critical roles for Polζin Cellular Tolerance to Yamazoe M. Nitric Oxide induced DNA Damage. (2006)
  • 著者名/発表者名: Xiaohua W, Takenaka K, Sonoda E, Hochegger H, Kawanishi S, Kawamoto T, Takeda S
  • 雑誌名: C a n c e r R e s. 66 ページ: 748-54
  • 査読あり
• [雑誌論文] Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells. (2005)
  • 著者名/発表者名: Nojima K, Hochegger H, Saberi A, Fukushima T, Kikuchi K, Yoshimura M, Orelli BJ, Bishop DK, Hirano S, Ohzeki M, Ishiai M, Yamamoto K, Takata M, Arakawa H, Buerstedde JM, Yamazoe M, Kawamoto T, Araki K, Takahashi JA, Hashimoto N, Takeda S, Sonoda E.
  • 雑誌名: C a n c e r R e s. 65 ページ: 11704-11
  • 査読あり
• [雑誌論文] Rad51 paralog deficiency on Similar effects of Brca2 truncation and immunoglobulin V gene diversification in DT40 cells support an early role for Rad51 paralogs in homologous recombination. (2005)
  • 著者名/発表者名: Hatanaka A, Yamazoe M, Sale J.E., Takata M, Yamamoto K, Kitao H, Sonoda E, Kikuchi K, Yonetani Y, Takeda S.
  • 雑誌名: M o l C e l l B i o l. 25 ページ: 1124-34
  • 査読あり
• [雑誌論文] in Homologous DNA Recombination Dual Roles for DNA Polymerase h and Translesion DNA Synthesis. (2005)
  • 著者名/発表者名: Kawamoto T, Araki K, Sonoda E, Yamashita, Y.M., Harada, K.K., Kikuchi1, K., Masutani, C., Hanaoka, F., Nozaki, K., Hashimoto, N., Takeda, S.
  • 雑誌名: M o l C e l l. 20 ページ: 793-9
  • 査読あり
• [学会発表] Interactions between the RNF8 and RAD18 " Differential Functional E3 ubiquitin ligases in Translesion DNA Synthesis and DSB Repair " (2010)
  • 著者名/発表者名: Takeda S
  • 学会等名: EMBO-Recombination Mechanism
  • 発表場所: Il Ciocco, Italy(発表予定だったが、直前に家族の事情によりキャンセル)
  • 年月日: 20100517-20100520
• [学会発表] Detect Environmental Mutagens and to "Chemical Genetic Method to Screen Anti-Malignant Chemical Compounds " (2009)
  • 著者名/発表者名: Takeda S
  • 学会等名: The 40th International Symposium of the Princess Takamatsu Cancer Research Fund
  • 発表場所: Hotel Grand Palace, Tokyo
  • 年月日: 20091110-20091112
• [学会発表] DNA polymerases in TLS" Gordon Research "Reverse Genetic Analysis of Conference (2009)
  • 著者名/発表者名: Takeda S
  • 学会等名: Colby-Sawyer College, New London
  • 発表場所: New Hampshire, USA
  • 年月日: 20090809-20090814
• [学会発表] RAD51 mediators, BRCA1, BRCA2, RAD51 "Reverse Genetic Study of paralogs, RAD52, Sws1, and Sfr1" (2009)
  • 著者名/発表者名: Takeda S
  • 学会等名: FASEB Genetic Recombination and Genome Rerrangements
  • 発表場所: Snowmass Village, Colorado, USA
  • 年月日: 20090802-20090807
• [学会発表] repair-deficient chicken DT40 cell "A novel approach using DNA lines for screening and characterizing the genotoxicity of chemical compounds and environmental contaminants" (2009)
  • 著者名/発表者名: Takeda S
  • 学会等名: Chromosome Dynamics and Genome Stability, Villars sur Ollon
  • 発表場所: Switzerland
  • 年月日: 20090514-20090516
• [学会発表] response by ubiquitin ligases " DNA (2009)
  • 著者名/発表者名: Takeda S
  • 学会等名: Regulation of DNA damage Repair
  • 発表場所: Crete, Greece
  • 年月日: 20090420-20090423
• [学会発表] Ubiquitin-Conjugating Enzymes Ubc13 and " A Critical Role for the RNF8 in Homologous Recombination " (2009)
  • 著者名/発表者名: Takeda S
  • 学会等名: Gordon Research Conference
  • 発表場所: Ventura, USA
  • 年月日: 20090208-20090213