Analyses of functional roles of TLS polymerases using transgenic mice
Project/Area Number |
22249005
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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 |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
YOKOI Masayuki 学習院大学, 理学部, 助教 (00322701)
AKAGI Jun-ichi 国立医薬品食品衛生研究所, 病理部, 研究員 (60512556)
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Project Period (FY) |
2010-04-01 – 2013-03-31
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥48,750,000 (Direct Cost: ¥37,500,000、Indirect Cost: ¥11,250,000)
Fiscal Year 2012: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2011: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2010: ¥22,750,000 (Direct Cost: ¥17,500,000、Indirect Cost: ¥5,250,000)
|
Keywords | 遺伝子ノックアウト / 損傷乗り越え複製 / 紫外線 / DNAポリメラーゼ / 突然変異 / 損傷トレランス / TLSポリメラーゼ / DNAポリメラーゼκ / REV1 / ノックアウトマウス / (6-4)光産物 / DNA損傷トレランス / DNAポリメラーゼ・イータ / 紫外線感受性 |
Research Abstract |
In order to examine the functional roles of translesion synthesis (TLS) in mammalian cells, we have established many mouse embryonic fibroblast cell lines expressing polymerase activity-defective or Rev1 interaction-defective mutant DNA polymerase eta (Pol eta) in Pol eta, Pol iota or Pol kappa single-, double- or triple-deficient mouse embryonic fibroblasts (MEFs). Using these MEF cells, we investigated UV sensitivity as well as mutation frequency upon UV irradiation. Our results suggest that there is an error-prone TLS pathway that uses Pol kappa via Rev1 in the absence of Pol eta.
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Report
(4 results)
Research Products
(61 results)
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[Journal Article] The vital role of polζand REV1 in mutagenic, but not correct, DNA synthesis across benzo[a]pyrene-dG and the recruitment of polζby REV1 to a replication-stalled site2012
Author(s)
Hashimoto, K., Cho, Y., Yang, I. Y., Akagi, J., Ohashi, E., Tateishi, S., de Wind, N., Hanaoka, F., Ohmori, H., and Moriya, M
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Journal Title
J. Biol. Chem.
Volume: 96
Pages: 9613-9622
Related Report
Peer Reviewed
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[Journal Article] NBS1 recruits RAD18 via aRAD6-like domain and regulates Polη-dependent translesion DNA synthesis2011
Author(s)
Yanagihara H, Kobayashi J, Tateishi S, Kato A, Matsuura S, Tauchi H, Yamada K, Takezawa J, Sugasawa K, Masutani C, Hanaoka F, Weemaes CM, Mori T, Zou L, Komatsu K.
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Journal Title
Mol Cell
Volume: 43
Issue: 5
Pages: 788-797
DOI
Related Report
Peer Reviewed
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[Journal Article] Genetic analysis using a mouse cell cycle mutant identifies magoh as a novel gene involved in Cdk regulation2011
Author(s)
Inaki, M., Kato, D., Utsugi, T., Onoda, F., Hanaoka, F., and Murakami, Y
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Journal Title
Genes Cells
Volume: 16
Issue: 2
Pages: 166-178
DOI
Related Report
Peer Reviewed
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[Journal Article] Photosensitized [2 + 2] cycloaddition on N-acetylated cytosine affords stereoselective formation of cyclobutane pyrimidine dimer2011
Author(s)
Yamamoto, J., Nishiguchi, K., Manabe, K., Masutani, C., Hanaoka, F., and Iwai, S
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Journal Title
Nucleic Acid Res
Volume: 39
Issue: 3
Pages: 1165-1175
DOI
Related Report
Peer Reviewed
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[Journal Article] Simultaneous disruption of two DNA polymerases, Polηand Polζin avian DT40 cells unmasks the role of Polηin celluler response to various DNA lesions2010
Author(s)
Hirota, K., Sonoda, E., Kawamoto, T., Motegi, A., Masutani, C., Hanaoka, F., Szuts, D., Iwai, S., Sale, J. E., Lehmann, A., and Takeda, S
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Journal Title
PLoS Genet
Volume: 6, pii
Issue: 10
Pages: e1001151-e1001151
DOI
Related Report
Peer Reviewed
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[Journal Article] Characterization of a Y-family DNA polymeraseηfrom the eukaryotic thermophile Alvinella pompejana2010
Author(s)
Kashiwagi, S., Kuraoka, I., Fujiwara, Y., Hitomi, K., Cheng, Q. J., Shin, D. S., Masutani, C., Tainer, J. A., Hanaoka, F., and Iwai, S
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Journal Title
J. Nucleic Acids pii
Volume: 2010
Pages: 701472-701472
DOI
Related Report
Peer Reviewed
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[Journal Article] Stimulation of DNA glycosylase activities by XPC protein complex : roles of protein-protein interactions2010
Author(s)
Shimizu, Y., Uchimura, Y., Dohmae, N., Saitoh, H., Hanaoka, F., and Sugasawa, K
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Journal Title
J. Nucleic Acids pii
Volume: 2010
Pages: 805698-805698
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Structure and mechanism of human DNA polymeraseη2010
Author(s)
Biertümpfel, C., Zhao, Y., Kondo, Y., Ramon-Maiques, S., Gregory, M., Lee, J. Y., Masutani, C., Lehmann, A. R., Hanaoka, F., and Yang, W
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Journal Title
Nature
Volume: 465
Issue: 7301
Pages: 1044-1049
DOI
Related Report
Peer Reviewed
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[Journal Article] Structure and mutagenesis studies of the C-terminal region of licensing factor Cdt1 enable to identify the key residues for binding to replicative helicase Mcm proteins2010
Author(s)
Jee, J.-G., Mizuno, T., Kamada, K., Tochio, T., Chiba, Y., Yanagi, K., Yasuda, G., Hiroaki, H., Hanaoka, F. and Shirakawa, M
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Journal Title
Journal of Biological Chemistry
Volume: vol.285(21)
Issue: 21
Pages: 15931-40
DOI
Related Report
Peer Reviewed
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[Presentation]2014
Author(s)
Osakabe, A., Tachiwana, H., Horikoshi, N., Kagawa, W., Yasuda, T., Hanaoka, F., Sugasawa, K., Iwai, S., and Kurumizaka, H
Organizer
International Conference, Kyoto, 2014: Replication, Repair and Recombination; coupling mechanisms and chromatin dynamics for genome integrity
Place of Presentation
京都
Related Report
Invited
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[Presentation] All road leads to DNA-lesion bypass : mechanisms of translesion synthesis2014
Author(s)
Yang, W., Lee, Young-Sam, Zhao, Y., Nakamura, T., Biertümpfel, C., Yamagata, Y., Hua, Y., and Hanaoka, F
Organizer
International Conference, Kyoto, 2014: Replication, Repair and Recombination; coupling mechanisms and chromatin dynamics for genome integrity
Place of Presentation
京都
Related Report
Invited
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[Presentation] Physiological role of TLS polymerases in mouse skin upon UV irradiation2014
Author(s)
Yokoi, M., Sakurai, Y., Hando, N., Morita, D., and Hanaoka, F
Organizer
International Conference, Kyoto, 2014: Replication, Repair and Recombination; coupling mechanisms and chromatin dynamics for genome integrity
Place of Presentation
京都
Related Report
Invited
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[Presentation] Regulation of DNA damage tolerance distinct from Polη-mediated translesion synthesis2014
Author(s)
Kanao, R., Masuda, Y., Hanaoka, F., and Masutani, C
Organizer
International Conference, Kyoto, 2014: Replication, Repair and Recombination; coupling mechanisms and chromatin dynamics for genome integrity
Place of Presentation
京都
Related Report
Invited
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[Presentation] Biochemical properties and structure of human DNA polymerase &eta, xeroderma pigmentosum variant- responsible gene product2011
Author(s)
Hanaoka, F., Kondo, Y., Masutani, C., Biertümpfel, C., Zhao, Y., Yang, W
Organizer
GDRI France Japan Conference
Place of Presentation
Montpellier, France
Related Report
Invited
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