Analysis of DNA repair pathway by the combination of proteomics andgenetic approach

• Project/Area Number: 22687001
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Genetics/Genome dynamics
• Research Institution: Tokyo Metropolitan University (2012); Kyoto University (2010-2011)
• Principal Investigator: HIROTA Kouji 首都大学東京, 大学院・理工学研究科, 教授 (00342840)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000); Fiscal Year 2012: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2011: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2010: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
• Keywords: DNA修復 / DNA損傷応答 / クロマチン / ユビキチン / がん / SILAC / DNA / ヒストン修飾 / DT40

Research Abstract

In this study, we analyzed ubiquitylation signal pathway in DNA repair using the combination of proteomics and genetic approach. Our data figure out novel ubiquitin signal pathway, which is useful seeds targets for cancer chemotherapy.

Research Products

• [Journal Article] nterference in DNA replication can cause mitotic chromosomal breakage unassociated with double-strand breaks (2013)
  • Author(s): FujitaM, Sasanuma H, Yamamoto K.N, Harada H, Kurosawa A, Adachi N, Omura M, Hiraoka M, Takeda S, Hirota K
  • Journal Title: PLOS ONE
• [Journal Article] Structure-specific endonucleases Xpf and Mus81 play overlapping but essential roles in DNA repair by homologous recombination (2013)
  • Author(s): Kikuchi, K, Narita, T., Van, P.T., Iijima, J., Hirota, K., Keka, I.S.,Mohiuddin, Okawa, K., Hori, T., Fukagawa, T., Essers, J., Kanaar, R.,Whitby, M.C., Sugasawa, K., Taniguchi, Y., Kitagawa, K., and Takeda, S
  • Journal Title: Cancer Research
• [Journal Article] Interference in DNA replication can cause mitotic chromosomal breakage unassociated with double-strand breaks (2013)
  • Author(s): Fujita M
  • Journal Title: PLOSONE Volume: 8
  • Peer Reviewed
• [Journal Article] Structure-specific endonucleases Xpf and Mus81 play overlapping but essential roles in DNA repair by homologous recombination. (2013)
  • Author(s): Kikuchi K
  • Journal Title: Cancer research Volume: in press
  • Peer Reviewed
• [Journal Article] A Central Coupler for Recombination Initiation Linking Chromosome Architecture to S Phase Checkpoint (2012)
  • Author(s): Miyoshi T, Ito M, Kugou K, Yamada S, Furuichi M, Oda A, Yamada T, Hirota K,Masai H, Ohta K
  • Journal Title: Mol. Cell Volume: 47(5) Pages: 722-733
• [Journal Article] A central coupler for recombination initiation linking chromosome architecture to S phase checkpoint. (2012)
  • Author(s): Miyoshi T
  • Journal Title: Mol Cell. Volume: 47 Pages: 722-733
  • Peer Reviewed
• [Journal Article] The USP1/UAF1 Complex Promotes Double-Strand Break Repair through Homologous Recombination. (2011)
  • Author(s): J. Murai, K. Yang, D. Dejsuphong, K. Hirota, S. Takeda and A. D. D'Andrea
  • Journal Title: Molecular and cellular biology Volume: 31 Pages: 2462-2469
• [Journal Article] The Epistatic Relationship between BRCA2 and the Other RAD51 Mediators in Homologous Recombination. (2011)
  • Author(s): Y. Qing, M. Yamazoe, K. Hirota, D. Dejsuphong, W.Sakai, K. N. Yamamoto, D. K. Bishop, X. Wu and S. Takeda
  • Journal Title: PLoS genetics Volume: 7
  • NAID: 120003338841
• [Journal Article] Characterization of environmental chemicals with potential for DNA damage using isogenic DNA repair-deficient chicken DT40 cell lines (2011)
  • Author(s): K. N. Yamamoto, K. Hirota, K. Kono, S. Takeda, S. Sakamuru,M. Xia, R. Huang, C. P. Austin, K. L. Witt and R. R. Tice
  • Journal Title: Environmental and molecular mutagenesis
• [Journal Article] Involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway. (2011)
  • Author(s): K. N. Yamamoto, S. Kobayashi, M. Tsuda, H. Kurumizaka, M. Takata, K. Kono, J. Jiricny, S. Takeda and K. Hirota
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 108 Pages: 6492-6496
  • NAID: 120003072120
• [Journal Article] Purification of the human SMN-GEMIN2 complex and assessment of its stimulation of RAD51-mediated DNA recombination reactions (2011)
  • Author(s): Tskaku M., Tsujita T., Horikoshi N., Takizawa Y., Qing Y., Hirota K., Ikura T., Takeda S., *Kurumizaka H
  • Journal Title: Biochemistry Volume: 32 Pages: 6797-6805
• [Journal Article] The involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway (2011)
  • Author(s): Yamamoto KN, Kobayashi S, Tsuda M, Kurumizaka H, Takata M, Kono K, Jiricny J, Takeda S, Hirota K
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108 Issue: 16 Pages: 6492-6496
  • DOI: 10.1073/pnas.1018487108
  • NAID: 120003072120
  • Peer Reviewed
• [Journal Article] The USP1/UAF1 complex promotes double-strand break repair through homologous recombination (2011)
  • Author(s): Murai J, et al
  • Journal Title: Mol Cell Biol Volume: 31 Issue: 12 Pages: 2462-2469
  • DOI: 10.1128/mcb.05058-11
  • Peer Reviewed
• [Journal Article] Characterization of environmental chemicals with potential for DNA damage using isogenic DNA repair-deficient chicken DT40 cell lines (2011)
  • Author(s): Yamamoto KN, Hirota K, Kono K, Takeda S, Sakamuru S, Xia M, Huang R, Austin CP, Witt KL, Tice RR
  • Journal Title: Environ Mol Mutagen Volume: 57 Issue: 7 Pages: 547-561
  • DOI: 10.1002/em.20656
  • Peer Reviewed
• [Journal Article] Purification of the Human SMN-GEMIN2 Complex and Assessment of Its Stimulation of RAD51-Mediated DNA Recombination Reactions (2011)
  • Author(s): Motoki Takaku, Takashi Tsujita, Naoki Horikoshi, Yoshimasa Takizawa, Yong, Qing, Kouji Hirota, Masae Ikura, Tsuyoshi Ikura, Shunichi Takeda, Hitoshi Kurumizaka
  • Journal Title: Biochemistry Volume: 50 Issue: 32 Pages: 6797-6805
  • DOI: 10.1021/bi200828g
  • Peer Reviewed
• [Journal Article] The epistatic relationship between BRCA2 and the other RAD51 mediators in homologous recombination (2011)
  • Author(s): Qing Y, et al
  • Journal Title: PLoS Genet Volume: 7 Issue: 7 Pages: e1002148-e1002148
  • DOI: 10.1371/journal.pgen.1002148
  • Peer Reviewed
• [Journal Article] Mutant cells defective in DNA repair pathways provide a sensitive high-throughput assay for genotoxicity (2010)
  • Author(s): T. J. Evans, K. N. Yamamoto, K. Hirota and S.Takeda
  • Journal Title: DNA repair 9 Pages: 1292-1298
  • NAID: 120002696050
• [Journal Article] Simultaneous disruption of two DNA polymerases, Poleta and Polzeta, in Avian DT40 cells unmasks the role of Poleta in cellular response to various DNA lesions (2010)
  • Author(s): K. Hirota, E. Sonoda, T. Kawamoto, A. Motegi, C. Masutani, F. Hanaoka, D. Szuts, S. Iwai, J. E. Sale, A.Lehmann and S. Takeda
  • Journal Title: PLoS genetics Volume: 6
• [Journal Article] DNA polymerases nu and theta are required for efficient immunoglobulin V gene diversification in chicken (2010)
  • Author(s): M. Kohzaki, K. Nishihara, K. Hirota, E. Sonoda, M. Yoshimura, S. Ekino, J. E. Butler, M. Watanabe, T. D. Halazonetis and S. Takeda
  • Journal Title: The Journal of cell biology Volume: 189 Pages: 1117-1127
• [Journal Article] Human replicative DNA polymerase delta can bypass T-T (6-4) ultraviolet photoproducts on template strands (2010)
  • Author(s): T. Narita, T. Tsurimoto, J. Yamamoto, K. Nishihara, K. Ogawa, E. Ohashi, T. Evans, S. Iwai, S. Takeda and K. Hirota
  • Journal Title: Genes Cells Volume: 15 Pages: 1228-1239
• [Journal Article] The roles of stress-activated Sty1 and Gcn2 kinases and of the protooncoprotein homologue Int6/eIF3e in responses to endogenous oxidative stress during histidine starvation (2010)
  • Author(s): N. Nemoto, T. Udagawa, T. Ohira, L. Jiang, K. Hirota, C. R. Wilkinson, J. Bahler, N. Jones, K. Ohta, R. C. Wek and K. Asano
  • Journal Title: Journal of molecular biology Volume: 404 Pages: 183-201
• [Journal Article] GEMIN2 promotes accumulation of RAD51 at double-strand breaks in homologous recombination (2010)
  • Author(s): Y. Takizawa, Y. Qing, M. Takaku, T. Ishida, Y. Morozumi, T. Tsujita, T. Kogame, K. Hirota, M. Takahashi, T. Shibata, H. Kurumizaka and S. Takeda
  • Journal Title: Nucleic acids research
• [Journal Article] KIAA1018/FAN1 nuclease protects cells against genomic instability induced by interstrand cross-linking agents (2010)
  • Author(s): K. Yoshikiyo, K. Kratz, K. Hirota, K. Nishihara, M. Takata, H. Kurumizaka, S. Horimoto, S. Takeda and J. Jiricny
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 107 Pages: 21553-21557
• [Journal Article] Mutant cells defective in DNA repair pathways provide a sensitive high-throughput assay for genotoxicity. (2010)
  • Author(s): T.J.Evans, K.N.Yamamoto, K.Hirota, S.Takeda.
  • Journal Title: DNA Repair (Amst) Volume: 9 Pages: 1292-8
  • NAID: 120002696050
  • Peer Reviewed
• [Journal Article] Simultaneous disruption of two DNA polymerases, Poleta and Polzeta, in Avian DT40 cells unmasks the role of Poleta in cellular response to various DNA lesions. (2010)
  • Author(s): K.Hirota, E.Sonoda, T.Kawamoto, A.Motegi, C.Masutani, F.Hanaoka, D.Szuts, S.Iwai, J.E.Sale, A.Lehmann, S.Takeda.
  • Journal Title: PLoS Genet Volume: 6
  • Peer Reviewed
• [Journal Article] DNA polymerases nu and theta are required for efficient immunoglobulin V gene diversification in chicken. (2010)
  • Author(s): M.Kohzaki, K.Nishihara, K.Hirota, E.Sonoda, M.Yoshimura, S.Ekino, J.E.Butler, M.Watanabe, T.D.Halazonetis, S.Takeda.
  • Journal Title: J Cell Biol Volume: 189 Pages: 1117-27
  • Peer Reviewed
• [Journal Article] Human replicative DNA polymerase delta can bypass T-T (6-4) ultraviolet photoproducts on template strands (2010)
  • Author(s): T.Narita, T.Tsurimoto, J.Yamamoto, K.Nishihara, K.Ogawa, E.Ohashi, T.Evans, S.Iwai, S.Takeda, K.Hirota.
  • Journal Title: Genes Cells Volume: 15 Pages: 1228-39
  • Peer Reviewed
• [Journal Article] The roles of stress-activated Sty1 and Gcn2 kinases and of the protooncoprotein homologue Int6/eIF3e in responses to endogenous oxidative stress during histidine starvation (2010)
  • Author(s): N.Nemoto, T.Udagawa, T.Ohira, L.Jiang, K.Hirota, C.R.Wilkinson, J.Bahler, N.Jones, K.Ohta, R.C.Wek, K.Asano.
  • Journal Title: J Mol Biol Volume: 404 Pages: 183-201
  • Peer Reviewed
• [Journal Article] GEMIN2 promotes accumulation of RAD51 at double-strand breaks in homologous recombination. (2010)
  • Author(s): Y.Takizawa, Y.Qing, M.Takaku, T.Ishida, Y.Morozumi, T.Tsujita, T.Kogame, K.Hirota, M.Takahashi, T.Shibata, H.Kurumizaka, S.Takeda., S.Takeda.
  • Journal Title: Nucleic Acids Res. Volume: 15 Pages: 5059-74
  • Peer Reviewed
• [Journal Article] KIAA1018/FAN1 nuclease protects cells against genomic instability induced by interstrand cross-linking agents. (2010)
  • Author(s): K.Yoshikiyo, K.Kratz, K.Hirota, K.Nishihara, M.Takata, H.Kurumizaka, S.Horimoto, S.Takeda, J.Jiricny.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 107 Pages: 21553-7
  • Peer Reviewed
• [Journal Article] The involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway. (2010)
  • Author(s): K.N.Yamamoto, S.Kobayashi, M.Tsuda, H.Kurumizaka, M.Takata, K.Kono, J.Jiricny, S.Takeda, K.Hirota.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: (In press)
  • NAID: 120003072120
  • Peer Reviewed
• [Presentation] 染色体断裂はいつもDNA2重鎖切断が原因とは限らない (2013)
  • Author(s): Hirota K
  • Organizer: 第72回日本癌学会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] SUMO-targetted Ubiquitin Ligase RNF4 Guards Genome Stability by suppressing error-prone Homologous Recombination (2012)
  • Author(s): Kouji Hirota at al
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 博多
  • Year and Date: 2012-12-14
• [Presentation] SUMO-targetted Ubiquitin Ligase RNF4 Guards Genome Stability by suppressing error-prone Homologous Recombination (2012)
  • Author(s): Hirota K
  • Organizer: 第３５回日本分子生物学会
  • Place of Presentation: 博多
  • Invited
• [Presentation] DNA Polymerase δ efficiently inserts nucleotides opposite abasic sites in vivo (2011)
  • Author(s): Narita T, et al., Hirota K
  • Organizer: 分子生物学会34回年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-16
• [Presentation] Gene regulation by lncRNAs in response to low glucose stress o (2011)
  • Author(s): Ohta K, et al
  • Organizer: 分子生物学会34回年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-16
• [Presentation] The involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway. (2011)
  • Author(s): Kouji Hirota at al.
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] The involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway (2011)
  • Author(s): Hirota K, et al
  • Organizer: 分子生物学会34回年会
  • Place of Presentation: パシフィコ横浜(招待講演)
  • Year and Date: 2011-12-15
• [Presentation] SMN-CEMIN2 complex stimulates the RAD51-mediated recombination reactions (2011)
  • Author(s): Takaku M, et al
  • Organizer: 分子生物学会34回年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-15
• [Presentation] DNAポリメラーゼδによるAP部位の損傷乗越え (2010)
  • Author(s): 廣田耕志
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Book] 血液内科領域における抗腫瘍薬の作用機序・副作用に基づく使い分け (2012)
  • Author(s): 笹沼博之、廣田耕志、武田俊
  • Publisher: シスプラチン耐性の分子機構 月刊血液内科
• [Book] 血液内科領域における抗腫瘍薬の作用機序・副作用に基づく使い分け シスプラチン耐性の分子機構 (2012)
  • Author(s): 笹沼博之
  • Total Pages: 6
  • Publisher: 月刊血液内科
• [Book] 廣田耕志、武田俊一 (2011)
  • Author(s): シスプラチン耐性の分子機構
  • Publisher: 医学の歩み
• [Book] 実験医学7月号長鎖ncRNAによるクロマチン・転写活性化の制御 (2011)
  • Author(s): 廣田耕志, 他
  • Total Pages: 6
  • Publisher: 羊土社
• [Book] 基礎の基礎 (2010)
  • Author(s): 廣田耕志、武田俊一
  • Publisher: 細胞工学
• [Remarks] プレスリリース発表2013 4/4DNAが切れていないのに発生する染色体断裂の発見-ヒトの被爆線量を測定する手法に異議あり-
  • URL: http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2013/130404_1.htm
• [Remarks] DNAが切れていないのに発生する染色体断裂の発見－ヒトの被爆線量を測定する手法に異議あり－
  • URL: http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2013/130404_1.htm