How Chromosomal Aberrations Are Induced by Telomere Dysfunction

2009 Fiscal Year Final Research Report

• Project/Area Number: 17013043
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: ISHIKAWA Fuyuki Kyoto University, 大学院・生命科学研究科, 教授 (30184493)
• Co-Investigator(Kenkyū-buntansha): URANO Takeshi 島根大学, 医学部, 教授 (70293701) ; NABETANI Akira 京都大学, 大学院・生命科学研究科, 助教 (40334495)
• Project Period (FY): 2005 – 2009
• Keywords: 染色体 / テロメア / クロマチン / テロメレース

Research Abstract

It is now well established that chromosomal aberrations play a major role in carcinogenesis. Yet, the precise mechanisms how aberrant chromosomes are formed remain unknown. In this study, we focused on the telomere, the terminal domain of linear chromosomes. First, we identified novel chromatin structures at telomeres, and next we examined how chromosomes would become unstable in dysfunctional telomeres.

Research Products

• [Journal Article] Alternative lengthening of telomeres pathway : recombination-mediated telomere maintenance mechanism in human cells. (2010)
  • Author(s): Nabetani, A., Ishikawa, F.
  • Journal Title: J Biochem 149 Pages: 5-14
• [Journal Article] ヘテロクロマチンとしてのテロメア (2010)
  • Author(s): 石川冬木
  • Journal Title: 化学と生物 48 Pages: 550-554
  • Peer Reviewed
• [Journal Article] テロメアの機能と構造 (2010)
  • Author(s): 石川冬木
  • Journal Title: 化学と生物 48 Pages: 493-497
• [Journal Article] テロメアと老化 (2010)
  • Author(s): 三河拓己、石川冬木
  • Journal Title: 血管医学 11 Pages: 111-116
• [Journal Article] Fission yeast Vps1 and Atg8 contribute to oxidative stress resistance. (2010)
  • Author(s): Mikawa, T., Kanoh, J., Ishikawa, F.
  • Journal Title: Genes Cells 15 Pages: 229-242
  • Peer Reviewed
• [Journal Article] RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway. (2009)
  • Author(s): Miyake, Y., Nakamura, M., Nabetani, A., Shimamura, S., Tamura, M., Yonehara, S., Saito, M., Ishikawa, F.
  • Journal Title: Mol Cell 36 Pages: 193-206
  • Peer Reviewed
• [Journal Article] A crucial role for adipose tissue p53 in the regulation of insulin resistance. (2009)
  • Author(s): Minamino, T., Orimo, M., Shimizu, I., Kunieda, T., Yokoyama, M., Ito, T., Nojima, A., Nabetani, A., Oike, Y., Matsubara, H., Ishikawa,F., Komurao, I.
  • Journal Title: Nat Med 15 Pages: 1082-1087
  • Peer Reviewed
• [Journal Article] Fission yeast Ku protein is required for recovery from DNA replication stress. (2009)
  • Author(s): Miyoshi, T., Kanoh, J., Ishikawa, F.
  • Journal Title: Genes Cells 14 Pages: 1091-1103
  • Peer Reviewed
• [Journal Article] 加齢のメカニズム:老化は遺伝子に刷り込まれているのか (2009)
  • Author(s): 石川冬木
  • Journal Title: 画像診断 29 Pages: 120-123
• [Journal Article] テロメアとゲノム安定性 (2009)
  • Author(s): 齊藤基輝、石川冬木
  • Journal Title: 日本臨牀(増刊) 67 Pages: 107-112
• [Journal Article] Unusual telomeric DNAs in human telomerase-negative immortalized cells. (2009)
  • Author(s): Nabetani, A., Ishikawa, F.
  • Journal Title: Mol Cell Biol 29 Pages: 703-713
  • Peer Reviewed
• [Journal Article] Interaction between DNMT1 and DNA replication reactions in the SV40 in vitro replication system. (2008)
  • Author(s): Shimamura, S., Ishikawa, F.
  • Journal Title: Cancer Sci 99 Pages: 1960-1966
  • Peer Reviewed
• [Journal Article] ヒトと分裂酵母で保存されたテロメアの最末端構造 (2008)
  • Author(s): 三好知一郎、石川冬木
  • Journal Title: 蛋白質・核酸・酵素 53 Pages: 1850-1857
• [Journal Article] 分裂酵母Pot1-Tpp1による染色体末端保護とテロメア長制御 (2008)
  • Author(s): 三好知一郎、石川冬木
  • Journal Title: 実験医学 26 Pages: 2601-2605
• [Journal Article] Fission yeastPot1-Tpp1 protects telomeres and regulates telomere length. (2008)
  • Author(s): Miyoshi, T., Kanoh, J., Saito, M., Ishikawa, F.
  • Journal Title: Science 320 Pages: 1341-1344
  • Peer Reviewed
• [Journal Article] Heterochromatin and RNAi are required to establish CENP-A chromatin at centromeres. (2008)
  • Author(s): Folco, H.D., Pidoux, A.L., Urano, T., Allshire, R.C.
  • Journal Title: Science 319 Pages: 94-97
  • Peer Reviewed
• [Journal Article] 細胞老化におけるヒストンH1の消失:細胞老化、アポトーシス、がんの抑制をつなぐ現象として注目 (2007)
  • Author(s): 舟山亮、石川冬木
  • Journal Title: 化学と生物 45 Pages: 740-742
• [Journal Article] ESE-3, an Ets family transcription factor, is up-regulated in cellular senescence. (2007)
  • Author(s): Fujikawa, M., Katagiri, T., Tugores, A., Nakamura, Y., Ishikawa, F.
  • Journal Title: Cancer Sci 98 Pages: 1468-1475
  • Peer Reviewed
• [Journal Article] がん抑制機構としての細胞老化の役割とクロマチンの構造変化 (2007)
  • Author(s): 舟山亮、石川冬木
  • Journal Title: 日本老年医学会雑誌 44 Pages: 546-550
• [Journal Article] Cellular senescence and chromatin structure. (2007)
  • Author(s): Funayama, R., Ishikawa, F.
  • Journal Title: Chromosoma 116 Pages: 431-440
• [Journal Article] Tel2 is required for activation of the Mrc1-mediated replication checkpoint. (2007)
  • Author(s): Shikata, M., Ishikawa, F., Kanoh, J.
  • Journal Title: J Biol Chem 282 Pages: 5346-5355
  • Peer Reviewed
• [Journal Article] Loss of linker histone H1 in cellular senescence. (2006)
  • Author(s): Funayama, R., Saito, M., Tanobe, H., Ishikawa, F.
  • Journal Title: J Cell Biol 175 Pages: 869-880
  • Peer Reviewed
• [Journal Article] Cellular senescence as a stress response. (2006)
  • Author(s): Ishikawa, F.
  • Journal Title: Cornea 25 Pages: S3-S6
• [Journal Article] 複製ストレスとテロメア (2006)
  • Author(s): 中村未来、西山敦哉、石川冬木
  • Journal Title: 蛋白質・核酸・酵素 51 Pages: 2245-2249
• [Journal Article] Nucleophosmin: a versatile molecule associated with hematological malignancies. (2006)
  • Author(s): Naoe, T., Suzuki, T., Kiyoi, H., Urano, T.
  • Journal Title: Cancer Sci 97 Pages: 963-969
  • Peer Reviewed
• [Journal Article] Cell-cycle-dependent regulation of telomere binding proteins : roles of Polo-like kinase. (2006)
  • Author(s): Nishiyama, A., Ishikawa, F.
  • Journal Title: Cell Cycle 5 Pages: 1403-1406
• [Journal Article] Cell-cycle-dependent Xenopus TRF1 recruitment to telomere chromatin regulated by Polo-like kinase. (2006)
  • Author(s): Nishiyama, A., Muraki, K., Saito, M., Ohsumi, K., Kishimoto, T., Ishikawa, F.
  • Journal Title: EMBO J 25 Pages: 575-584
  • Peer Reviewed
• [Journal Article] Alterations of DNA and chromatin structures at telomeres and genetic instability in mouse cells defective in DNA polymerase alpha. (2005)
  • Author(s): Nakamura, M., Nabetani, A., Mizuno, T., Hanaoka, F. Ishikawa, F.
  • Journal Title: Mol Cell Biol 25 Pages: 11073-11088
  • Peer Reviewed
• [Journal Article] なぜ老化因子は保存されているのか? (2005)
  • Author(s): 石川冬木
  • Journal Title: 実験医学 23 Pages: 2876-2879
• [Journal Article] Telomere binding protein Taz1 establishes Swi6 heterochromatin independently of RNAi at telomeres. (2005)
  • Author(s): Kanoh, J., Sadaie, M., Urano, T., Ishikawa, F.
  • Journal Title: Curr Biol 15 Pages: 1808-1819
  • Peer Reviewed
• [Journal Article] 進化における体細胞突然変異の意義 (2005)
  • Author(s): 石川冬木
  • Journal Title: 化学と生物 43 Pages: 531-537
• [Journal Article] RNA polymerase II is required for RNAi-dependent heterochromatin assembly. (2005)
  • Author(s): Kato, H., Goto, D.B., Martienssen, R.A., Urano, T., Furukawa, K., Murakami, Y.
  • Journal Title: Science 309 Pages: 467-469
  • Peer Reviewed
• [Presentation] Regulation of telomerase through Tel1ATM and/or Rad3ATR-mediated phosphorylation of the shelterin component Ccq1 in fission yeast. (2010)
  • Author(s): Fuyuki Ishikawa
  • Organizer: EMBO Conference Series 'Telomeres and the DNA Damage Response'.
  • Place of Presentation: The Hotel Pullman, Marseille, France
  • Year and Date: 2010-09-17
• [Presentation] Telomere metabolism during the cell cycle revealed by analyzing single telomeres in human cells. (2010)
  • Author(s): Fuyuki Ishikawa
  • Organizer: AACR Special Conference-The Role of Telomeres an Telomerase in Cancer Research.
  • Place of Presentation: The Worthington Renaissance Fort Worth Hotel, Fort Worth, Texas, U.S.A
  • Year and Date: 2010-03-01
• [Presentation] がん細胞悪性化の原動力としてのテロメア機能異常 (2010)
  • Author(s): 石川冬木
  • Organizer: 科学研究費補助金「特定領域研究」がん研究に係わる特定領域研究平成21年度5領域合同シンポジウム
  • Place of Presentation: 東京都、学術総合センター
  • Year and Date: 2010-01-15
• [Presentation] Low-Dose Stress Responses. (2009)
  • Author(s): Fuyuki Ishikawa
  • Organizer: The 5th International Fission Yeast meeting 'Pombe 2009'
  • Place of Presentation: National Olympics Memorial Youth Center, Tokyo
  • Year and Date: 2009-10-29
• [Presentation] RPA-like Mammalian Ctc1-Stn1-Ten1 Complex Binds to Single-Stranded DNA and Protects Telomeres Independently of the Pot1 Pathway. (2009)
  • Author(s): Yasuyuki Miyake, Mirai Nakamura, Akira Nabetani, Shoko Fujita, Shintaro Shimamura, Miki Tamura, Motoki Saito, Fuyuki Ishikawa
  • Organizer: Keystone Symposia on Molecular and Cellular Biology 'Telomere Biology and DNA Repair'.
  • Place of Presentation: RACV Royal Pines Resort, Queensland, Australia
  • Year and Date: 2009-10-10
• [Presentation] Unusual single-stranded telomeric DNA structures for telomere metabolism in human ALT cells. (2009)
  • Author(s): Akira Nabetani, Fuyuki Ishikawa
  • Organizer: 68th Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: Pasifico Yokohama Convention Center, Yokohama
  • Year and Date: 2009-10-03
• [Presentation] A novel RPA-like mammalian complex CST. (2009)
  • Author(s): Fuyuki Ishikawa
  • Organizer: French-Japanese Workshop in Life Sciences.
  • Place of Presentation: CNRS, Campus Gerard-Megie, Paris
  • Year and Date: 2009-09-22
• [Presentation] 「がん」はどのようにして起こるのか? (2009)
  • Author(s): 石川冬木
  • Organizer: 第5回文部科学省科学研究費補助金特定領域研究「がん特定」青少年・市民公開講座
  • Place of Presentation: 島根県出雲市、出雲市民会館
  • Year and Date: 2009-06-20
• [Presentation] Ctc1-Stn1-Ten1 complex. (2009)
  • Author(s): Fuyuki Ishikawa
  • Organizer: CSHL meeting 'Telomere and Telomerase'.
  • Place of Presentation: Cold Spring Harbor Laboratory, NY, U.S.A
  • Year and Date: 2009-04-29
• [Presentation] Sheltrin telomere complex. (2008)
  • Author(s): Fuyuki Ishikawa
  • Organizer: 67th Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: Nagoya Congress Center, Nagoya
  • Year and Date: 2008-10-28
• [Presentation] Shelterin complex in fission yeast. (2008)
  • Author(s): Fuyuki Ishikawa
  • Organizer: EMBO Conference 2008 "Telomeres and the DNA damage response"
  • Place of Presentation: Eurotel Victoria Villars, Villars- sur-Ollon, Switzerland
  • Year and Date: 2008-09-18
• [Presentation] Shelterin complex in fission yeast. (2008)
  • Author(s): Fuyuki Ishikawa
  • Organizer: Internal seminar of Institut de Genetique Humaine, CNRS (Host : Marcel Mechali)
  • Place of Presentation: CNRS, Montpellier, France
  • Year and Date: 2008-09-10
• [Presentation] Shelterin complex in fission yeast. (2008)
  • Author(s): Fuyuki Ishikawa
  • Organizer: Internal seminar of Institut de Biologie Structurale et Microbiologie, CNRS (Host : Vincent Geli)
  • Place of Presentation: CNRS, Marseille, France
  • Year and Date: 2008-09-08
• [Presentation] 低容量ストレス (2008)
  • Author(s): 石川冬木
  • Organizer: 東京大学先端科学技術センターセミナー
  • Place of Presentation: 東京都、東京大学先端科学技術センター
  • Year and Date: 2008-04-25
• [Presentation] 染色体の最末端構造と制御 (2007)
  • Author(s): 石川冬木
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会BMB2007
  • Place of Presentation: 横浜市、パシフィコ横浜
  • Year and Date: 2007-12-14
• [Presentation] How cells sense their telomere lengths? (2007)
  • Author(s): Fuyuki Ishikawa
  • Organizer: The 66th Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: Pasifico Yokohama Convention Center, Yokohama
  • Year and Date: 2007-10-03
• [Presentation] The Extreme Terminus of Chromosomes. (2007)
  • Author(s): Tomoichiro Miyoshi, Motoki Saito, Junko Kanoh, Fuyuki Ishikawa
  • Organizer: The 79th Annual Meeting of the Genetics Society of Japan.
  • Place of Presentation: Okayama University, Okayama
  • Year and Date: 2007-09-21
• [Presentation] 生命はどのようにして進化したのか (2007)
  • Author(s): 石川冬木
  • Organizer: 第28回宇宙ステーション利用計画ワークショップ:きぼうから始まる未来
  • Place of Presentation: 東京都、学術総合センター
  • Year and Date: 2007-08-07
• [Presentation] The Extreme Terminus of Chromosomes. (2007)
  • Author(s): Fuyuki Ishikawa
  • Organizer: Fourth International Fission Yeast Meeting, Pombe2007.
  • Place of Presentation: Copenhagen University, Copenhagen, Denmark
  • Year and Date: 2007-06-13
• [Presentation] The Pot1 complex maintains telomere integrity in fission yeast. (2007)
  • Author(s): Fuyuki Ishikawa
  • Organizer: CSHL meeting 'Telomere and Telomerase'
  • Place of Presentation: Cold Spring Harbor Laboratory, NY, U.S.A
  • Year and Date: 2007-05-04
• [Presentation] 細胞老化:ストレス反応としてのがん抑制機構 (2007)
  • Author(s): 石川冬木
  • Organizer: 第27回日本医学会総会
  • Place of Presentation: 大阪市、大阪国際会議場
  • Year and Date: 2007-04-06
• [Presentation] 染色体末端構造 (2006)
  • Author(s): 石川冬木
  • Organizer: がん特定領域研究発がん分野A01/A02合同研究発表会
  • Place of Presentation: 倉敷市、せとうち児島ホテル
  • Year and Date: 2006-12-02
• [Presentation] がん細胞とは何か? (2006)
  • Author(s): 石川冬木
  • Organizer: がん特定領域研究高等学校対象出前講義
  • Place of Presentation: 徳島市、徳島市立高等学校
  • Year and Date: 2006-11-20
• [Presentation] Altered Balance of Linker-DNA Binding Proteins in Cellular Senescence. (2006)
  • Author(s): Fuyuki Ishikawa
  • Organizer: Josef Steiner-CNIO Cancer Conference : Telomeres & Telomerase.
  • Place of Presentation: Spanish National Cancer Research Centre, Madrid, Spain
  • Year and Date: 2006-11-13
• [Presentation] 細胞老化におけるクロマチン構造の変化 (2006)
  • Author(s): 石川冬木
  • Organizer: 情報伝達系北海道研究会
  • Place of Presentation: 札幌市、札幌アスペンホテル
  • Year and Date: 2006-11-03
• [Presentation] 染色体テロメアの構造と機能 (2006)
  • Author(s): 石川冬木
  • Organizer: 第51回日本人類遺伝学会大会
  • Place of Presentation: 米子市、米子コンベンションセンター
  • Year and Date: 2006-10-19
• [Presentation] ヒトはどうして老化するのか (2006)
  • Author(s): 石川冬木
  • Organizer: 西宮市ライフサイエンスセミナー
  • Place of Presentation: 西宮市、夙川公民館
  • Year and Date: 2006-10-13
• [Presentation] 非致死的ストレスによる染色体不安定化 (2006)
  • Author(s): 石川冬木
  • Organizer: 第65回日本癌学会学術総会
  • Place of Presentation: 横浜市、パシフィコ横浜国際会議場
  • Year and Date: 2006-09-29
• [Presentation] Histone H1 loss in cellular senescence. (2006)
  • Author(s): Fuyuki Ishikawa
  • Organizer: Internal seminar of University of Geneva.
  • Place of Presentation: University of Geneva, Geneva, Switzerland
  • Year and Date: 2006-09-04
• [Presentation] The Pot1 complex maintains telomere integrity in fission yeast. (2006)
  • Author(s): Fuyuki Ishikawa
  • Organizer: International Symposium 'Telomeres and Genome Stability'.
  • Place of Presentation: Eurotel Victoria, Villars-sur-Ollon, Switzerland
  • Year and Date: 2006-08-31
• [Presentation] Histone H1 loss in cellular senescence. (2006)
  • Author(s): Fuyuki Ishikawa
  • Organizer: Internal seminar of Friedrich Miescher Institute.
  • Place of Presentation: Friedrich Miescher Institute, Basel, Switzerland
  • Year and Date: 2006-08-29
• [Presentation] Ageing, Cancer and Sex. (2006)
  • Author(s): Fuyuki Ishikawa
  • Organizer: JSPS 11th Japanese-German Symposium `Frontiers of Cancer Research'.
  • Place of Presentation: Ringhotel Munte am Stadtwald, Bremen, Germany
  • Year and Date: 2006-04-21
• [Presentation] Reproduction Strategies And Configurations Of Genetic Materials. (2006)
  • Author(s): Fuyuki Ishikawa
  • Organizer: The 52nd NIBB Conference : Reproductive Strategies.
  • Place of Presentation: National Institute for Basic Biology, Okazaki, Aichi
  • Year and Date: 2006-01-21
• [Presentation] Telomere Functions in DNA Replication and End Protection. (2005)
  • Author(s): Fuyuki Ishikawa
  • Organizer: Cancer Research in Korea and Japan .the Past and Coming Decade.
  • Place of Presentation: Tokyo Uniberisty, Tokyo
  • Year and Date: 2005-12-17
• [Presentation] ストレスと老化 (2005)
  • Author(s): 石川冬木
  • Organizer: 第28回分子生物学会年会市民公開講座「生命のからくりを分子でみる-遺伝子・病気・老化をテーマに-」
  • Place of Presentation: 福岡市、福岡エルガーラホール
  • Year and Date: 2005-12-11
• [Presentation] Cellular Senescence as a Stress Response. (2005)
  • Author(s): Fuyuki Ishikawa
  • Organizer: Kyoto Cornea Club.
  • Place of Presentation: Westin Miyako Kyoto Hotel, Kyoto
  • Year and Date: 2005-12-02
• [Presentation] ストレスに対するクロマチン反応としての老化 (2005)
  • Author(s): 石川冬木
  • Organizer: 千里ライフサイエンスセミナー「老化」
  • Place of Presentation: 豊中市、千里ライフサイエンスセンタービル
  • Year and Date: 2005-11-22
• [Presentation] Stress Responses at Telomeres. (2005)
  • Author(s): Fuyuki Ishikawa
  • Organizer: International Symposium on Ran and Cell Cycle.
  • Place of Presentation: Awaji Yumebutai International Conference Center, Awaji, Hyogo
  • Year and Date: 2005-10-02
• [Presentation] Stress Responses of Chromatin. (2005)
  • Author(s): Fuyuki Ishikawa
  • Organizer: 10th Japanese-German Workshop on Molecukar and Cellular Aspects of Carnigo Genesis.
  • Place of Presentation: Weisser Saal, Essen, Germany
  • Year and Date: 2005-09-29
• [Presentation] クロマチンの安定性と発がん過程 (2005)
  • Author(s): 石川冬木
  • Organizer: 第64回日本癌学会学術総会教育講演:モーニングレクチャー
  • Place of Presentation: 札幌市・ロイトン札幌ホテル
  • Year and Date: 2005-09-16
• [Book] がん化学療法・分子標的治療update(テロメアとテロメラーゼ)(西條長宏、西尾和人(編集)) (2009)
  • Author(s): 山崎晴丈、石川冬木
  • Publisher: 中外医学社
• [Book] がんの分子標的治療(テロメア長制御と末端保護機能:shelterin複合体)(鶴尾隆(編集)) (2008)
  • Author(s): 石川冬木
  • Publisher: 南山堂