Cellular responses to inhibition of DNA replication fork progression at DNA lesions
Project/Area Number |
19209003
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biological pharmacy
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Research Institution | Gakushuin University (2008-2009) Osaka University (2007) |
Principal Investigator |
HANAOKA Fumio Gakushuin University, 理学部, 教授 (50012670)
|
Co-Investigator(Kenkyū-buntansha) |
MASUTANI Chikahide 大阪大学, 生命機能研究科, 准教授 (40241252)
OHKUMO Tuyoshi 大阪大学, 生命機能研究科, 助教 (50432505)
|
Project Period (FY) |
2007 – 2009
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Project Status |
Completed (Fiscal Year 2009)
|
Budget Amount *help |
¥49,920,000 (Direct Cost: ¥38,400,000、Indirect Cost: ¥11,520,000)
Fiscal Year 2009: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2008: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2007: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000)
|
Keywords | 遺伝子 / 癌 / DNA複製 / 放射線 / ゲノム / クロマチン / 細胞周期 / がん |
Research Abstract |
We studied how eukaryotic cells respond to various DNA damages that prevent the progression of DNA replication fork. We found that one of the translesion DNA synthesis polymerase, DNA polymerase η, interacts with several other repair proteins such as mismatch repair proteins, is phosphorylated and ubiquitinated at certain amino acid residues, and changes the intracellular localization upon UV irradiation. We demonstrated that the template-switching mechanism is operating not only in prokaryotes but also in higher eukaryotes.
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Report
(4 results)
Research Products
(67 results)
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[Journal Article] Structure and mechanism of human DNA polymeraseη2010
Author(s)
Biertumpfel, C., Zhao, Y., Kondo, Y., Ramon-Maiques, S., Gregory, M., Lee, J.Y., Masutani, C., Lehmann, A.R., Hanaoka, F., Yang, W
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Journal Title
Nature 465
Pages: 44-1049
Related Report
Peer Reviewed
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[Journal Article] Structure and mutagenesis studies of the C-terminal region of licensing factor Cdt1 enable the identification of key residues for binding to replicative helicase Mcm proteins.2010
Author(s)
Jee, J., Mizuno, T., Kamada, K., Tochio, H., Chiba, Y., Yanagi, K.I., Yasuda, G., Hiroaki, H., Hanaoka, F., Shirakawa, M.
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Journal Title
J. Biol. Chem 285
Pages: 15931-15940
Related Report
Peer Reviewed
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[Journal Article] Polymerization by DNA polymerase eta is blocked by cisdiamminedichloroplatinum( II) 1, 3-d(GpTpG) cross-link: implications for cytotoxic effects in nucleotide excision repair-negative tumor cells.2010
Author(s)
Chijiwa, S., Masutani, C., Hanaoka, F., Iwai, S., Kuraoka, I
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Journal Title
Carcinogenesis 31
Pages: 388-393
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Peer Reviewed
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[Journal Article] The molecular chaperone Hsp90 regulates accumulation of DNA polymerase eta at replication stalling sites in UV-irradiated cells.2010
Author(s)
Sekimoto, T., Oda, T., Pozo, F.M., Murakumo, Y., Masutani, C., Hanaoka, F., Yamashita, T
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Journal Title
Mol. Cell 37
Pages: 79-89
Related Report
Peer Reviewed
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[Journal Article] Critical amino acids in human DNA polymerases eta and kappa involved in erroneous incorporation of oxidized nucleotides.2010
Author(s)
Katafuchi, A., Sassa, A., Niimi, N., Gruz, P. Fujimoto, H., Masutani, C., Hanaoka, F., Ohta, T., Nohmi, T.
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Journal Title
Nucleic Acids Res 38
Pages: 859-867
Related Report
Peer Reviewed
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[Journal Article] The chromosomal association of condensin II is required by a noncatalytic function of PP2A.2009
Author(s)
Takemoto, A., Maeshima, K., Ikehara, T., Yamaguchi, K., Murayama, A., Imamura, S., Imamoto, N., Yokoyama, S., Hirano, T., Watanabe, Y., Hanaoka, F., Yanagisawa, J., Kimura, K
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Journal Title
Nat. Struct. Mol. Biol 16
Pages: 1302-1308
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Peer Reviewed
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[Journal Article] Eukaryotic DNA polymerases alpha, beta and epsilon incorporate guanine opposite 2, 2, 4-triamino-5(2H)-oxazolone.2009
Author(s)
Kino, K., Sugasawa, K., Mizuno, T., Bando, T., Sugiyama, H., Akita, M., Miyazawa, H., Hanaoka, F.
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Journal Title
Chembiochem 10
Pages: 2613-2616
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Peer Reviewed
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[Journal Article] Translesional DNA synthesis through a C8-guanyl adduct of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) in vitro: REV1 inserts dC opposite the lesion, and DNA polymerase kappa potentially catalyzes extension reaction from the 3'-dC terminus.2009
Author(s)
Fukuda, H., Takamura-Enya, T., Masuda, Y., Nohmi, T., Seki, C., Kamiya, K., Sugimura, T., Masutani, C., Hanaoka, F., Nakagama, H.
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Journal Title
J. Biol. Chem 284
Pages: 25585-25592
Related Report
Peer Reviewed
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[Journal Article] UV-DDB-dependent regulation of nucleotide excision repair kinetics in living cells.2009
Author(s)
Nishi, R., Alekseev, S., Dinant, C., Hoogstraten, D., Houtsmuller, A.B., Hoeijmakers, J.H., Vermeulen, W., Hanaoka, F., Sugasawa, K.
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Journal Title
DNA Repair 8
Pages: 767-776
Related Report
Peer Reviewed
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[Journal Article] Interaction with DNA polymerase eta is required for nuclear accumulation of REV1 and suppression of spontaneous mutations in human cells.2009
Author(s)
Akagi, J., Masutani, C., Kataoka, Y., Kan, T., Ohashi, E., Mori, T., Ohmori, H., Hanaoka, F.
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Journal Title
DNA Repair 8
Pages: 585-599
Related Report
Peer Reviewed
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[Journal Article] Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases.2009
Author(s)
Kimura, T., Takeuchi, T., Kumamoto-Yonezawa, Y., Ohashi, E., Ohmori, H., Masutani, C., Hanaoka, F., Sugawara, F., Yoshida, H., Mizushina, Y.
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Journal Title
Bioorg. Med. Chem 17
Pages: 1811-1816
Related Report
Peer Reviewed
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[Journal Article] Cyclin A-Cdk1 regulates the origin firing program in mammalian cells.2009
Author(s)
Katsuno, Y., Suzuki, A., Sugimura, K., Okumura, K., Zineldeen, D.H., Shimada, M., Niida, H., Mizuno, T., Hanaoka, F., Nakanishi, M.
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Journal Title
Proc. Natl. Acad. Sci. USA 106
Pages: 3184-3189
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[Journal Article] DNA polymerase eta is a limiting factor for A:T mutations in Ig genes and contributes to antibody affinity maturation.2008
Author(s)
Masuda, K., Ouchida, R., Yokoi, M., Hanaoka, F., Azuma, T., Wang, J.Y.
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Journal Title
Eur. J. Immunol 38
Pages: 796-2805
Related Report
Peer Reviewed
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[Journal Article] Novel DNA microarray system for analysis of nascent mRNAs.2008
Author(s)
Ohtsu, M., Kawate, M., Fukuoka, M., Gunji, W., Hanaoka, F., Utsugi, T., Onoda, F., Murakami, Y.
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Journal Title
DNA Res 15
Pages: 241-251
Related Report
Peer Reviewed
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[Journal Article] Genetic analysis reveals an intrinsic property of the germinal center B cells to generate A:T mutations.2008
Author(s)
Ouchida, R., Ukai, A., Mori, H., Kawamura, K., Dolle, M.E.T., Tagawa, M., Sakamoto, A., Tokuhisa, T., Yokosuka, T., Saito, T., Yokoi, M., Hanaoka, F., Vijg, J., Wang, J.Y.
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Journal Title
DNA Repair 7
Pages: 1392-1398
Related Report
Peer Reviewed
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[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.
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Journal Title
Genes Cells 13
Pages: 343-354
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Peer Reviewed
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[Journal Article] Miscoding properties of 2'-deoxyinosine, a nitric oxide-derived DNA adduct, during translesion synthesis catalyzed by human DNA polymerases.2008
Author(s)
Yasui, M., Suenaga, E., Koyama, N., Masutani, C., Hanaoka, F., Gruz, P., Shibutani, S., Nohmi, T., Hayashi, M., Honma, M.
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Journal Title
J. Mol. Biol 377
Pages: 1015-1023
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Peer Reviewed
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[Journal Article] Specificity of mutations induced by incorporation of oxidized dNTPs into DNA by human DNA polymerase eta.2008
Author(s)
Hidaka, K., Yamada, M., Kamiya, H., Masutani, C., Harashima, H., Hanaoka, F., Nohmi, T.
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Journal Title
DNA Repair 7
Pages: 497-506
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Peer Reviewed
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[Journal Article] Mutagenic radioadaptation in a human lymphoblastoid cell line.2008
Author(s)
Yatagai, F., Umebayashi, Y., Homma, M., Sugasawa, K., Takayama, Y., Hanaoka, F.
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Journal Title
Mutat. Res 638
Pages: 48-55
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[Journal Article] In vivo destabilization and functional defects of the xeroderma pigmentosum C protein caused by a pathogenic missense mutation.2007
Author(s)
Yasuda, G., Nishi, R., Watanabe, E., Mori, T., Iwai, S., Orioli, D., Stefanini, M., Hanaoka, F., Sugasawa, K.
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Journal Title
Mol. Cell. Biol 27
Pages: 6606-6614
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Peer Reviewed
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[Journal Article] Dicer-related drh-3 gene functions in germ-line development by maintenance of chromosomal integrity in Caenorhabditis elegans.2007
Author(s)
Nakamura, M., Ando, R., Nakazawa, T., Yudazono, T., Tsutsumi, N., Hatanaka, N., Ohgake, T., Hanaoka, F., Eki, T.
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Journal Title
Genes Cells 12
Pages: 997-1010
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Peer Reviewed
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[Journal Article] A second PCNA loader complex, Ctf18-RFC, stimulates DNA polymeraseηactivity.2007
Author(s)
Shiomi, Y., Masutani, C., Hanaoka, F., Kimura, H., Tsurimoto, T.
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Journal Title
J. Biol. Chem 282
Pages: 20906-20914
Related Report
Peer Reviewed
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[Journal Article] DNA polymeraseηand・function in the same genetic pathway to generate mutations at A/T during somatic hypermutation of Ig genes.2007
Author(s)
Masuda, K., Ouchida, R., Hikida, M., Kurosaki, T., Yokoi, M., Masutani, C., Seki, M., Wood, R.D., Hanaoka, F., O-Wang, J.
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Journal Title
J. Biol. Chem 282
Pages: 17387-17394
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Peer Reviewed
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[Journal Article] 2-Hydroxy-dATP enhances A:T→C:G mutations caused by 8-hydroxy-dGTP by suppressing its degradation upon replication in a HeLa extract.2007
Author(s)
Satou, K., Kasai, H., Masutani, C., Hanaoka, F., Harashima, H., Kamiya, H.
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Journal Title
Biochemistry 46
Pages: 6639-6646
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Peer Reviewed
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[Journal Article] Efficient and erroneous incorporation of oxidized DNA precursors by human DNA polymeraseη.2007
Author(s)
Shimizu, M., Gruz, P., Kamiya, H., Masutani, C., Xu, Y., Usui, Y., Sugiyama, H., Harashima, H., Hanaoka, F., Nohmi, T.
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Journal Title
Biochemistry 46
Pages: 5515-5522
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[Journal Article] Analysis of the role of Aurora B on the chromosomal targeting of condensin I.2007
Author(s)
Takemoto, A., Murayama, A., Katano, M., Urano, T., Furukawa, K., Yokoyama, S., Yanagisawa, J., Hanaoka, F., Kimura, K.
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Journal Title
Nucleic Acids Res 35
Pages: 2403-2412
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Peer Reviewed
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[Journal Article] A kinase subunit of the human mediator complex, CDK8, positively regulates transcriptional activation.2007
Author(s)
Furumoto, T., Tanaka, A., Ito, M., Malik, S., Hirose, Y., Hanaoka, F., Ohkuma, Y.
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Journal Title
Genes Cells 12
Pages: 119-132
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[Journal Article] Aberrant DNA polymerase alpha is excluded from the nucleus by defective import and degradation in the nucleus.
Author(s)
Eichinger, C.S., Mizuno, T., Mizuno, K., Miyake, Y., Yanagi, K., Imamoto, N., Hanaoka, F.
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Journal Title
J. Biol. Chem 284
Pages: 30604-30614
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