Functions of RecQ family helicases in DNA replication, repair, and damage avoidance

2009 Fiscal Year Final Research Report

• Project/Area Number: 17013005
• 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: ENOMOTO Takemi Tohoku University, 大学院・薬学研究科, 教授 (80107383)
• Project Period (FY): 2005 – 2009
• Keywords: 癌 / ブルーム症候群 / ロスモンド・トムソン症候群 / RecQファミリーへリカーゼ / DNA複製 / DNA組換え / 姉妹染色分体接着

Research Abstract

Human cells possess five RecQ family helicases, RECQL1, BLM, WRN, RTS, and RECQL5, whose defects cause a predisposition to cancer. In this study, functions of these RecQ family helicases were investigated and following results were obtained. BLM functions at the last stage of DNA replication, segregation of replicated DNA and sister chromatid cohesion. RTS is involved in DNA replication and repair of DNA double strand breaks. Finally, RECQL1 and RECQL5 are involved in early stages of recombination.

Research Products

• [Journal Article] RecQL5 promotes genome stabilization trough two parallel mechanisms-Interacting with RNA polymerase II and acting as a helicase (2010)
  • Author(s): Islam, M.N., Fox. D. III, Guo, R., Enomoto, T., Wang, W
  • Journal Title: Mol. Cell. Biol 30 Pages: 2460-2472
  • Peer Reviewed
• [Journal Article] Global analysis of mutual interaction surfaces of nucleosomes with comprehensive point mutants (2009)
  • Author(s): Sakamoto, M., Noguchi, S., Kawashima, S., Okada, Y., Enomoto, T., Seki, M., Horikoshi, M
  • Journal Title: Genes Cells 14 Pages: 1271-1330
  • Peer Reviewed
• [Journal Article] Structure of the Cdt1 C-terminal domain: conservation of the winged helix fold in replication licensing factors (2009)
  • Author(s): Khayrutdinov, B.I., Bae, W.J., Yun, Y.M., Lee, J.H., Tsuyama, T., Kim. J.J., Hwang, E., Ryu, K.S., Cheong, H.K., Cheong, C., Ko, J.S., Enomoto, T., Karplus, P.A., Guntert. P., Tada, S., Jeon, Y.H., Cho, Y
  • Journal Title: Protein Sci 18 Pages: 2252-2264
  • Peer Reviewed
• [Journal Article] Effect of heliquinomycin on the activity of human MCM4/6/7 helicase (2009)
  • Author(s): Ishimi, Y., Sugiyama, T., Nakaya, R., Kanamori, M., Kohno, T., Enomoto, T., Chino, M
  • Journal Title: FEBS J 276 Pages: 3382-3391
  • Peer Reviewed
• [Journal Article] Accumulation of sumoylated Rad52 in checkpoint mutants perturbed in DNA replication (2009)
  • Author(s): Ohuchi, T., Seki, M., Kugou, K., Tada, S., Ohta, K., Enomoto, T
  • Journal Title: DNA Repair 8 Pages: 690-696
  • Peer Reviewed
• [Journal Article] Alternative title: Generation and characterization of cells that can be conditionally depleted of mitochondrial SOD2 (2009)
  • Author(s): Takada, S., Inoue, E., Tano, K., Yoshii, H., Abe, T., Yoshimura, A., Akita, M., Tada, S., Watanabe, M., Seki, M., Enomoto, T
  • Journal Title: Biochem. Biophys. Res. Commun 379 Pages: 233-238
  • Peer Reviewed
• [Journal Article] Repression of nascent strand elongation by deregulated Cdt1 during DNA replication in Xenopus egg extracts (2009)
  • Author(s): Tsuyama, T., Watanabe, S., Aoki, A., Cho, Y., Seki, M., Enomoto, T., Tada, S
  • Journal Title: Mol. Bio. Cell 20 Pages: 937-947
  • Peer Reviewed
• [Journal Article] A novel function for Rad17 in homologous recombination (2008)
  • Author(s): Nishino, K., Inoue, E., Takada, S., Abe, T., Akita, M., Yoshimura, A., Tada, S., Kobayashi, M., Yamamoto, K., Enomoto, T
  • Journal Title: Genes Genet. Syst 83 Pages: 427-431
  • Peer Reviewed
• [Journal Article] RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability (2008)
  • Author(s): Xu, D., Guo, R., Sobeck, A., Bachrati, C.Z., Yang, J., Enomoto, T., Brown, G.W., Hoatlin, M.E., Hickson, I.D., Wang W
  • Journal Title: Gene Dev 22 Pages: 2843-2855
  • Peer Reviewed
• [Journal Article] KU70/80, DNA-PKcs, and Artemis are essential for the rapid induction of apoptosis after massive DSB formation (2008)
  • Author(s): Abe, T., Ishiai, M., Hosono, Y., Yoshimura, A., Tsuji, H., Tada, S., Adachi, N., Koyama, H., Takata, M., Takeda, S., Enomoto, T., Seki, M
  • Journal Title: Cell Signal 20 Pages: 1978-1985
  • Peer Reviewed
• [Journal Article] Nuclear localization of Rad52 is pre-requisite for its sumoylation (2008)
  • Author(s): Ohuchi, T., Seki, M., Enomoto, T
  • Journal Title: Biochem. Biophys. Res. Commun 372 Pages: 126-130
  • Peer Reviewed
• [Journal Article] Rad52 sumoylation and its involvement in the efficient induction of homologous recombination (2008)
  • Author(s): Ohuchi, T., Seki, M., Branzei, D., Maeda, D., Ui, A., Ogiwara, H., Tada, S., Enomoto, T
  • Journal Title: DNA Repair 7 Pages: 879-889
  • Peer Reviewed
• [Journal Article] Analyses of functional interaction between RECQL1, RECQL5, and BLM which physically interact with DNA topoisomerase III・ (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: 75-8
  • 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: Nuc. Acids Res 35 Pages: 4989-5000
  • Peer Reviewed
• [Journal Article] Rmi1, a member of the Sgs1-Top3 complex in budding yeast, contributes to sister chromatid cohesion (2007)
  • Author(s): Lai M.S., Seki, M., Ui, A., Enomoto, T
  • Journal Title: EMBO Reports 8 Pages: 685-690
  • Peer Reviewed
• [Journal Article] Activation of a novel pathway involving Mms1 and Rad59 in sgs1 cells (2007)
  • Author(s): Ui, A., Seki, M., Ogiwara, H., Lai, M.S., Yamamoto, K., Tada, S., Enomoto, T
  • Journal Title: Biochem. Biophys. Res. Commun 356 Pages: 1031-1037
  • Peer Reviewed
• [Journal Article] 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 construction (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: Nuc. Acids Res 35 Pages: 3109-3117
  • Peer Reviewed
• [Journal Article] 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] Ames test-negative carcinogen, ortho-phenyl phenol, binds tubulin and causes aneuploidy in budding yeast (2007)
  • Author(s): Nunoshiba, T., Watanabe, E., Takahashi, T., Daigaku., Y., Ishikawa, S., Mochizuki, M., Ui, A., Enomoto, T., Yamamoto, K
  • Journal Title: Mut. Res 617 Pages: 90-97
  • 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
  • Peer Reviewed
• [Journal Article] Possible involvement of RecQL4 in the repair of double-strand DNA breaks in Xenopus egg extracts (2007)
  • Author(s): Kumata, Y., Tada, S., Yamanada, Y., Tsuyama, T., Kobayashi, T., Dong, Y. -P., Ikegami, K., Murofushi, H., Seki, M., Enomoto, T
  • Journal Title: Biochim. Biophys. Acta 1773 Pages: 556-564
  • Peer Reviewed
• [Journal Article] Chl1 and Ctf4 are required for damage-induced recombinations. Biochem (2007)
  • Author(s): Ogiwara, H., Ui, A., Lai M.S., Enomoto, T., Seki M
  • Journal Title: Biophys. Res. Commun 354 Pages: 222-226
  • Peer Reviewed
• [Journal Article] Role of Elg1 protein in the double-strand breaks repair (2007)
  • Author(s): Ogiwara, H., Ui, A., Enomoto, T., Seki, M
  • Journal Title: Nuc. Acids Res 35 Pages: 353-362
  • Peer Reviewed
• [Journal Article] Chromatin loading of Smc5/6 is induced by DNA replication but not by DNA double-strand breaks (2006)
  • Author(s): Tsuyama, T., Inou, K., Seki, M., Seki, T., Kumata, Y., Kobayashi, T., Kimura, K., Hanaoka, F., Enomoto, T., Tada, S
  • Journal Title: Biochem. Biophys. Res. Commun 351 Pages: 935-939
  • Peer Reviewed
• [Journal Article] Mgs1 and Rad18/Rad5/Mms2 are required for survival of novel temperature/cold sensitive mutant alleles of Pol31, the second subunit of DNA polymerase・, in Saccharomyces cerevisiae (2006)
  • Author(s): Davoodi Vijeh Motlagh, N., Branzei, D., Seki, M., Enomoto, T
  • Journal Title: DNA Repair 5 Pages: 1459-1474
  • Peer Reviewed
• [Journal Article] A novel Rad18 function involved in the protection of the vertebrate genome after exposure to camptothecin (2006)
  • Author(s): Yoshimura, A., Nishino, K., Takezawa, J., Tada, S., Kobayashi, T., Sonoda, E., Kawamoto, T., Takeda, S., Ishii, Y., Yamada, K., Enomoto, T., Seki, M
  • Journal Title: DNA Repair 5 Pages: 1307-1316
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] BLM is an early responder to DNA double-strand breaks. Biochem. Biophys (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: Res. Commun 348 Pages: 62-69
  • Peer Reviewed
• [Journal Article] Loss of heterozygosity in yeast can occur by ultraviolet irradiation during the S phase of the cell cycle (2006)
  • Author(s): Daigaku, Y., Mashiko, S., Mishiba, K., Yamamura, S., Ui, A., Enomoto, T., Yamamoto, K
  • Journal Title: Mutat. Res 600 Pages: 177-183
  • Peer Reviewed
• [Journal Article] Bloom helicase and DNA topoisomerase III・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
  • Peer Reviewed
• [Journal Article] Dpb11, the budding yeast homologue of TopBP1, functions with the checkpoint clamp in recombination repair (2006)
  • Author(s): Ogiwara, H., Ui, A., Onoda, F., Tada, S., Enomoto, T., Seki, M
  • Journal Title: Nuc. Acids Res 34 Pages: 3389-3398
  • Peer Reviewed
• [Journal Article] Caenorhabditis elegans geminin homologue participates in cell cycle regulation and germ line development (2005)
  • Author(s): Yanagi, K., Mizuno, T., Tsuyama, T., Tada, S., Iida, Y., Sugimoto, A., Eki, T., Enomoto, T., Hanaoka F
  • Journal Title: J. Biol. Chem 280 Pages: 19689-19694
  • Peer Reviewed
• [Journal Article] Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM (2005)
  • Author(s): Hirano, S., Yamamoto, K., Ishiai, M., Yamazoe, M., Seki, M., Matsushita, N., Ohzeki, M., Yamashita, Y.M., Arakawa, H., Buerstedde, J. -M., Enomoto, T., Takeda, S., Thompson, L.H., Takata, M
  • Journal Title: EMBO J 24 Pages: 418-427
  • Peer Reviewed
• [Journal Article] Human Werner helicase interacting protein 1 (WRNIP1) functions as a novel modulator for DNA polymerase・・ (2005)
  • Author(s): Tsurimoto, T., Shinozaki, A., Yano, M., Seki, M., Enomoto, T
  • Journal Title: Genes Cells 10 Pages: 13-22
  • Peer Reviewed
• [Journal Article] DNA topoisomerase III is essential for damage-induced recombination (2005)
  • Author(s): Ui, A., Seki, M., Ogiwara, H., Onodera, R., Fukushige, S., Onoda, F., Enomoto, T
  • Journal Title: DNA Repair 4 Pages: 191-201
  • Peer Reviewed
• [Presentation] The role of FACT in DNA replication (2009)
  • Author(s): Takemi Enomoto
  • Organizer: Swiss-Japan joint metting on the molecular mechanisms regulating "Chromosome dynamics and Genome stability"
  • Place of Presentation: Villars Ollons, Switzerland
  • Year and Date: 2009-05-15
• [Presentation] ブルーム症候群原因遺伝子産物BLMのDNA複製及び姉妹染色分体接着における役割(Functions of the Bloom syndrome responsible gene product in DNA replication and sister chromatid cohesion) (2008)
  • Author(s): 榎本武美
  • Organizer: 日本環境変異原学会第37回大会
  • Place of Presentation: 沖縄
  • Year and Date: 2008-12-05
• [Presentation] Rmi1, a member of the Sgs1-Top3 complex in budding yeast, contributes to sister chromatid cohesion (2008)
  • Author(s): Mong Sing Lai, Masayuki Seki, Ayako Ui, Takemi Enomoto
  • Organizer: 2008 EMBO conference on DNA recombination
  • Place of Presentation: Cioccol, Italy
  • Year and Date: 2008-05-21
• [Presentation] RecQL4のDNA二本鎖切断誘発時における挙動の解析 (2008)
  • Author(s): 池上京子、多田周右、Li Lan、安井明、関政幸、榎本武美
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-27
• [Presentation] Illegitimate activation of Cdt1 at S-phase possibly leads to a halt of nascent strand elongation in DNA re-replication (2007)
  • Author(s): Shusuke Tada, Masayuki Seki, Takemi Enomoto
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] BLM functions together with XRCC3 for resumption of stalled replication forks (2006)
  • Author(s): Makoto Otsuki, Masayuki Seki, Eri Inoue, Genta Katoh, Akari Yoshimura, Shusuke Tada, Yutaka Ishii, Shunichi Takeda, Takemi Enomoto
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB congress
  • Place of Presentation: Kyoto
  • Year and Date: 2006-06-18
• [Presentation] Rmi1/Nce4, a subunit of the Sgs1-Top3 complex of Saccharomyces cerevisiae is involved in homologous recombination and establishment of sister chromatid cohesion (2006)
  • Author(s): Mong Sing Lai、宇井彩子、関政幸、榎本武美
  • Organizer: 日本薬学会第126年会
  • Place of Presentation: 仙台
  • Year and Date: 2006-03-29
• [Presentation] DNA二本鎖切断修復におけるRecQL4の機能の解析 (2006)
  • Author(s): 山名田弓枝、多田周右、二藤望、熊田裕司、小林貴之、関政幸、榎本武美
  • Organizer: 日本薬学会第126年会
  • Place of Presentation: 仙台
  • Year and Date: 2006-03-28
• [Presentation] BLM is an early responder to DNA double strand breaks (2005)
  • Author(s): Parimal Karmakar, Masayuki Seki, Makoto Kanamori, Shusuke Tada, Li Lan, Kazunari Hashiguchi, Akira Yasui, Takemi Enomoto
  • Organizer: The 5th Symposium on DNA Replication, Recombination and Repair
  • Place of Presentation: Hyogo
  • Year and Date: 2005-11-13
• [Presentation] BLM acts together with XRCC3 upon damage induction (2005)
  • Author(s): Makoto Otsuki, Masayuki Seki, Genta Kato, Eri Inoue, Akari Yoshimura, Shusuke Tada, Takemi Enomoto
  • Organizer: 第78回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2005-10-22
• [Presentation] ブルーム症候群原因遺伝子産物の機能の解析 (2005)
  • Author(s): 関政幸、多田周右、榎本武美
  • Organizer: 第64回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2005-09-14
• [Book] 蛋白質核酸酵素別冊;染色体サイクル (2009)
  • Author(s): 関政幸・Mong Sing Lai・榎本武美
  • Total Pages: 543-546
  • Publisher: 共立出版
• [Book] Reviews and protocols in DT40 research (2006)
  • Author(s): Seki, M., Tada, S., Enomoto, T
  • Total Pages: 49-73
  • Publisher: Springer