The network regulating the chromosome cycle

2009 Fiscal Year Final Research Report

• Project/Area Number: 17080014
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: MASAI Hisao Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 参事研究員 (40229349)
• Co-Investigator(Kenkyū-buntansha): TURIMOTO Tosiki 九州大学, 大学院・理学研究科, 教授 (30163885) ; NIKI Hironori 国立遺伝子研究所, 系統生物研究センター, 教授 (70208122)
• Co-Investigator(Renkei-kenkyūsha): MASUKATA Hisao 大阪大学, 大学院・理学研究科, 教授 (00199689) ; SINOHARA Akira 大阪大学, 蛋白質研究所, 教授 (00252578)
• Project Period (FY): 2005 – 2009
• Keywords: DNA / クロマチン構造 / リン酸化 / 染色体サイクル / 染色体分配 / 染色体複製 / 組換え / 複製フォーク

Research Abstract

The chromosome, the carrier of genome DNA, undergoes a series of dynamic changes during the cell cycle. This "chromosome cycle" involves the interplay of DNA replication, segregation, recombination and genomic rearrangement, permitting faithful duplication of the genome and its stable inheritance. The goal of this project is to understand the molecular mechanisms underlying each of these processes and to elucidate how they are coordinated with each other to achieve the integrated and highly regulated progression of the chromosome cycle. The outcome of this project will not only reveal novel insights into chromosome cycle regulation but will also shed light on the mechanisms of how the dysfunction of the chromosome cycle leads to various diseases such as cancer, or to developmental abnormality and, potentially, to aging. During the research period, we have discovered many novel interplays between varied chromosome transactions, and disclosed important mechanistic aspect for regulation of DNA replication, recombination, and segregation of chromosomes and how they collaborate for the operation of the chromosome cycle.

Research Products

• [Journal Article] Deregulated Cdc6 inhibits DNA replication and suppresses Cdc7-mediated phosphorylation of Mcm2-7 complex. (2010)
  • Author(s): Kundu, L.R., Kumata, Y, Kakusho, N., Watanabe, S., Furukohri, A., Waga, S., Sekia, M., Masai, H., Enomoto, T., Tada, S.
  • Journal Title: Nucleic Acid Res. PMID(in press [Epub ahead of print]) Pages: 20421204
  • Peer Reviewed
• [Journal Article] Casein Kinase 2-dependent phosphorylation of human Rad9 mediates the interaction between human Rad9-Hus1-Rad1 complex and TopBP1. (2010)
  • Author(s): Takeishi, Y., Ohashi, E., Ogawa, K., Masai, H., Obuse, C., Tsurimoto, T.
  • Journal Title: Genes to Cells (in press)
  • Peer Reviewed
• [Journal Article] Eukaryotic DNA replication; where, when and how? (2010)
  • Author(s): Masai, H., Matsumoto, S., You, Z., Yoshizawa-Sugata, N., Oda, M.
  • Journal Title: Annual Rev. Biochem. PMID(in press. [Epub ahead of print]) Pages: 20373915
  • Peer Reviewed
• [Journal Article] The DNA damage checkpoint regulates a transition between yeast and hyphal growth in Schizosaccharomyces japonicus. (2010)
  • Author(s): Furuya K, Niki H.
  • Journal Title: Mol. Cell. Biol. (in press)
  • Peer Reviewed
• [Journal Article] Casein Kinase 2-dependent phosphorylation of human Rad9 mediates the interaction between human Rad9-Hus1-Rad1 complex and TopBP1. (2010)
  • Author(s): Takeishi Y, Ohashi E, Ogawa K, Masai H, Obuse C, Tsurimoto T.
  • Journal Title: Genes Cells (in press)
  • Peer Reviewed
• [Journal Article] Interactions between Swi1-Swi3, Mrc1 and S phase kinase, Hsk1 may regulate cellular responses to stalled replication forks in fission yeast. (2009)
  • Author(s): Shimmoto, S., Matsumoto, S., Hayano, M., Yokoyama, M., Noguchi, E., Russell, P., Masai, H.
  • Journal Title: Genes to Cells 14 Pages: 669-682.
  • Peer Reviewed
• [Journal Article] Replisome progression complex links DNA replication to sister chromatid cohesion in Xenopus egg extracts. (2009)
  • Author(s): Tanaka, H., Kubota, Y., Tsujimura, T., Kumano, M., Masai, H., Takisawa, H.
  • Journal Title: Genes to Cells 14 Pages: 949-63
  • Peer Reviewed
• [Journal Article] Roles of human AND-1 in chromosome transactions in S phase. (2009)
  • Author(s): Yoshizawa-Sugata, N., Masai, H.
  • Journal Title: J. Biol. Chem. 284 Pages: 20718-20728
  • Peer Reviewed
• [Journal Article] Isolation of heterothallic haploid and auxotroph mutants of Schizosaccharomyces japonicus. (2009)
  • Author(s): Furuya K, Niki H.
  • Journal Title: Yeast. 26 Pages: 221-233
  • Peer Reviewed
• [Journal Article] Replication initiator DnaA of Escherichia coli changes its assembly form on the replication origin during the cell cycle. (2009)
  • Author(s): Nozaki S, Niki, H, Ogawa, T.
  • Journal Title: J. Bacteriol. 191 Pages: 4807-4814
  • Peer Reviewed
• [Journal Article] A genome-scale proteomic screen identifies a role for DnaK in chaperoning of polar autotransporters in Shigella J. (2009)
  • Author(s): Janakiraman, A., Fixen, K.R., Gray, A.N. Niki, H., Goldberg, M.B.
  • Journal Title: Bacteriol. 191 Pages: 6300-6311
  • Peer Reviewed
• [Journal Article] Genetic mechanism regulating bacterial cell shape and metabolism (2009)
  • Author(s): Shiomi D, Mori, H, Niki, H.
  • Journal Title: Commu. & Integ. Biol. 2 Pages: 219-220
  • Peer Reviewed
• [Journal Article] Physical and functional interaction between WRNIP1 and RAD18. (2009)
  • Author(s): Yoshimura A, Seki M, Kanamori M, Takeishi S, Tsurimoto T, Tada S, Enomoto T.
  • Journal Title: Genes Genet. Syst. 84 Pages: 171-178
  • Peer Reviewed
• [Journal Article] Cdc7 kinase is required for Claspin phosphorylation in DNA replication checkpoint. (2008)
  • Author(s): Kim, J-M., Kakusho, N., Yamada, M., Kanoh, Y., Takemoto, N., Masai, H.
  • Journal Title: Oncogene 27 Pages: 3475-3482
  • Peer Reviewed
• [Journal Article] Cdc7-dependent phosphorylation of Mer2 facilitates initiation of yeast meiotic recombination. (2008)
  • Author(s): Sasanuma, H., Hirota, K., Fukuda, T., Kakusho, N., Kugou, N., Kawasaki, Y., Shibata, T., Masai, H., Ohta, K.
  • Journal Title: Genes & Dev. 22 Pages: 398-410
  • Peer Reviewed
• [Journal Article] Spatio-temporal dynamics of multicellular cell cycle progression. (2008)
  • Author(s): Sakaue-Sawano, A., Kurokawa, H., Morimura, T., Hanyu, A., Hama, H., Kashiwagi, S., Fukami, K., Imamura, T., Ogawa, M., Masai, H., Miyawaki, A.
  • Journal Title: Cell 132 Pages: 487-498
  • Peer Reviewed
• [Journal Article] Identification of stimulators and inhibitors of CDC7 kinase in vitro. (2008)
  • Author(s): Kakusho, N., Taniyama, C., Masai, H.
  • Journal Title: J. Biol. Chem. 283 Pages: 19211-19218
  • Peer Reviewed
• [Journal Article] Cdt1 forms a complex with MCM and activates its helicase activity. (2008)
  • Author(s): You, Z., Masai, H.
  • Journal Title: J. Biol. Chem. 283 Pages: 24469-24477
  • Peer Reviewed
• [Journal Article] Determination of bacterial rod shape by a novel cytoskeletal membrane protein. (2008)
  • Author(s): Shiomi D, Sakai M, Niki H.
  • Journal Title: EMBO. J 26 Pages: 3081-3091
  • Peer Reviewed
• [Journal Article] CDK inhibitor p21 is degraded by a PCNA coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation. (2008)
  • Author(s): Nishitani H, Shiomi Y, Iida H, Michishita M, Takami T Tsurimoto, T.
  • Journal Title: J Biol Chem. 283 Pages: 29045-29052
  • Peer Reviewed
• [Journal Article] DNA damage induced ubiquitylation of RFC2 subunit of RFC complex. (2008)
  • Author(s): Tomida J, Masuda Y, Hiroaki H, Ishikawa T, Song I, Tsurimoto T, Tateishi S, Shiomi T, Kamei Y, Kim J, Kamiya K, Vaziri C, Ohmori H, Todo T.
  • Journal Title: J Biol Chem. 283 Pages: 9071-9079
  • Peer Reviewed
• [Journal Article] Recognition of forked and single-stranded DNA structures by human RAD18 complexed with RAD6B protein triggers its recruitment to stalled replication forks. (2008)
  • Author(s): Tsuji Y, Watanabe K, Araki K, Shinohara M, Yamagata Y, Tsurimoto T, Hanaoka F, Yamamura K, Yamaizumi M, Tateishi, S.
  • Journal Title: Genes Cells 13 Pages: 343-354
  • Peer Reviewed
• [Journal Article] Human Tim/Timeless-interacting protein, Tipin, is required for efficient progression of S phase and DNA replication checkpoint. (2007)
  • Author(s): Yoshizawa-Sugata, N., Masai, H.
  • Journal Title: J. Biol. Chem. 282 Pages: 2729-2740
  • Peer Reviewed
• [Journal Article] Escherichia coli PriA protein: Two modes of DNA binding and activation of ATP hydrolysis. (2007)
  • Author(s): Tanaka, T., Mizukoshi, T., Sasaki, K., Kohda, D., Masai, H.
  • Journal Title: J. Biol. Chem. 282 Pages: 19917-19927
  • Peer Reviewed
• [Journal Article] Structural basis of the 3'-end recognition of a leding strand in stalled DNA replication forks by PriA. (2007)
  • Author(s): Sasaki, K., Ose, T., Okamoto, N., Maenaka, K., Tanaka, T., Masai, H., Saito, M., Shirai, T., D. Kohda
  • Journal Title: EMBO J. 26 Pages: 19917-19927
  • Peer Reviewed
• [Journal Article] The trans-envelope Tol-Pal complex is part of the cell division machinery and required for proper outer-membrane invagination during cell constriction in E. (2007)
  • Author(s): Gerding MA, Ogata Y, Pecora ND, Niki H, de Boer PA.
  • Journal Title: coli. Mol. Microbiol. 63 Pages: 1008-1025
  • Peer Reviewed
• [Journal Article] Escherichia coli with a linear genome. (2007)
  • Author(s): Cui T, Moro-oka N, Ohsumi K, Kodama K, Ohshima T, Ogasawara N, Mori H, Wanner B, Niki H, Horiuchi T.
  • Journal Title: EMBO Rep. 8 Pages: 181-187
  • Peer Reviewed
• [Journal Article] Oscillating focus of SopA associated with filamentous structure guides partitioning of F plasmid. (2007)
  • Author(s): Hatano, T., Yamaichi, Y., Niki, H.
  • Journal Title: Mol. Microbiol. 64 Pages: 1198-11213
  • Peer Reviewed
• [Journal Article] A second PCNA loader complex, Ctf18-RFC, stimulates DNA polymerase eta activity. (2007)
  • Author(s): Shiomi Y, Masutani C, Hanaoka F, Kimura H, Tsurimoto, T.
  • Journal Title: J Biol Chem. 282 Pages: 20906-20914
  • Peer Reviewed
• [Journal Article] Dynamics of human replication factors in the elongation phase of DNA replication. (2007)
  • Author(s): Masuda Y, Suzuki M, Piao J, Gu Y, Tsurimoto T, Kamiya K.
  • Journal Title: Nucleic Acids Res. 35 Pages: 6904-6916
  • Peer Reviewed
• [Journal Article] Rad3-Cds1 mediates coupling of initiation of meiotic recombination with DNA replication: Mei4-dependent transcription as a potential target of meiotic checkpoint. (2006)
  • Author(s): Ogino, K., Masai, H.
  • Journal Title: J. Biol. Chem. 281 Pages: 1338-1344
  • Peer Reviewed
• [Journal Article] Stabilization of a stalled replication fork by concerted actions of two helicases. (2006)
  • Author(s): Tanaka, T., Masai, H.
  • Journal Title: J. Biol. Chem. 281 Pages: 3484-3493
  • Peer Reviewed
• [Journal Article] Crystallization and preliminary crystallographic analysis of the N-terminal domain of PriA from Escherichia coli. (2006)
  • Author(s): Sasaki, K., Ose, T., Tanaka, T., Mizukoshi, T., Ishigaki, T., Maenaka, K., Masai, H., Kohda, D.
  • Journal Title: Biochim. Biophys. Acta. 1764 Pages: 157-160
  • Peer Reviewed
• [Journal Article] Nuclear import of Epstein-Barr Virus Nuclear Antigen 1 mediated by NPI-1 - and down-regulated by phosphorylation of the nuclear localization signal for which Lys379 and Arg380 are essential. (2006)
  • Author(s): Kitamura, R., Sekimoto, T., Ito, S., Harada, S., Yamagata, H., Masai, H., Yoneda, H., Yanagi, K.
  • Journal Title: J. Virol. 80 Pages: 979-1991
  • Peer Reviewed
• [Journal Article] Hsk1 kinase is required for induction of meiotic double-stranded DNA breaks without involving checkpoint kinases in fission yeast. (2006)
  • Author(s): Ogino, K., Hirota, K., Matsumoto, S., Takeda, T., Ohta, K., Arai, K., Masai, H.
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 8131-8136
  • Peer Reviewed
• [Journal Article] "Replication initiation from a novel origin identified in the Th2 cytokine cluster locus requires a distant conserved non-coding sequence. " (*cocommunicating authors) (2006)
  • Author(s): Hayashida, T., Oda, M., Ohsawa, K., Yamaguchi, A., Giacca, M., Locksley, R.M., Masai H., Miyatake, S. *
  • Journal Title: J. Immunol. 176 Pages: 5446-5454
  • Peer Reviewed
• [Journal Article] Phosphorylation of MCM4 by Cdc7 kinase facilitates its interaction with Cdc45 on the chromatin. (2006)
  • Author(s): Masai, H., Taniyama, C., Ogino, K., Matsui, E., Kakusho, N., Matsumoto, M., Kim, J-M., Ishii, A., Tanaka, T., Kobayashi, T., Tamai, K., Ohtani, K., Arai, K.
  • Journal Title: J. Biol. Chem. 281 Pages: 39249-32961
  • Peer Reviewed
• [Journal Article] Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. (2006)
  • Author(s): Nishitani H, Sugimoto N, Roukos V, Nakanishi Y, Saijo M, Obuse C, Tsurimoto T, Nakayama K-I, Nakayama K, Fujita M, Lygerou Z, Nishimoto T.
  • Journal Title: EMBO J. 25 Pages: 1126-1136
  • Peer Reviewed
• [Journal Article] proteins in Genomic Stability. (in DNA Replication and Human Disease ed. DePamphilis M L, Cold Spring Harbor Press NY) (2006)
  • Author(s): Tsurimoto T.
  • Journal Title: PCNA and RFC Pages: 411-434
  • Peer Reviewed
• [Journal Article] n Proliferating Cell Nuclear Antigen (PCNA) ed. Lee H. Research Signpost, Kerala, India (2006)
  • Author(s): Tsurimoto T.
  • Journal Title: PCNA-interacting proteins. Pages: 25-49
  • Peer Reviewed
• [Journal Article] Cell cycle and developmental regulations of replication factors in mouse embryonic stem cells. (2005)
  • Author(s): Fujii-Yamamoto, H., Kim, J-M., Arai, K., Masai, H.
  • Journal Title: J. Biol. Chem. 280 Pages: 12976-12987
  • Peer Reviewed
• [Journal Article] A second human Dbf4/ASK-related protein, Drf1/ASKL1 is required for efficient completion of S and M phases. (2005)
  • Author(s): Yoshizawa-Sugata, N., Ishii, A., Taniyama, C., Matsui, E., Arai, K., Masai, H.
  • Journal Title: J. Biol. Chem. 280 Pages: 13062-13070
  • Peer Reviewed
• [Journal Article] Functional analyses of mouse ASK, an activator subunit for Cdc7 kinase, using conditional ASK knockout ES cells. (2005)
  • Author(s): Yamashita, N., Kim, J-M., Koiwai, O., Arai, K., Masai, H.
  • Journal Title: Genes to Cells 50 Pages: 551-563
  • Peer Reviewed
• [Presentation] Factors Regulating the Origin Selection in Eukaryotic DNA Replication. (2009)
  • Author(s): Masai, H., Matsumoto, S., Hayano, M., Kanoh, Y., Yamazaki, S., Shimmoto, M., Kakusho, N., Kudo, S.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜(シンポジウム招待講演)
  • Year and Date: 20091209-20091212
• [Presentation] Cellular responses to stalled replication forks: roles of Cdc7 kinase and fork stabilization factors. (2009)
  • Author(s): Masai, H.
  • Organizer: 25th RBC International Symposium "Genomic Instability: mechanisms and diseases"
  • Place of Presentation: Kyoto (Invited Lecture)
  • Year and Date: 20091130-20091201
• [Presentation] Actions of Mcm helicase and fork stabilizing factors at replication forks (MCMヘリカーゼと複製フォーク安定化因子の生化学的解析) (2009)
  • Author(s): Masai, H., You, Z., Tanaka, T., Yokoyama, M.
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸(招待講演)
  • Year and Date: 20091022-20091024
• [Book] 染色体サイクルの連係的制御機構概論蛋白質核酸酵素増刊号「染色体サイクル」(正井久雄、升方久夫、釣本敏樹、仁木宏典、篠原彰編集) (2009)
  • Author(s): 正井久雄
  • Total Pages: 521-523
  • Publisher: 共立出版
• [Remarks]
  • URL: http://www.nig.ac.jp/labs/NigPrjct/sensai/vol01/index.html