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Novel DNA damage responses and repair regulated by poly-ADP ribosylation and chromatin remodeling

Research Project

Project/Area Number 20241011
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionTohoku University

Principal Investigator

YASUI Akira  東北大学, 加齢医学研究所, 教授 (60191110)

Co-Investigator(Kenkyū-buntansha) NAKAJIMA Satoshi  東北大学, 加齢医学研究所, 助教 (00375114)
KANNO Shinichirou  東北大学, 加齢医学研究所, 講師 (10400417)
TANAKA Kouzo  東北大学, 加齢医学研究所, 准教授 (00304452)
TAKAO Masashi  東北大学, 加齢医学研究所, 講師 (70216612)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥49,140,000 (Direct Cost: ¥37,800,000、Indirect Cost: ¥11,340,000)
Fiscal Year 2010: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2009: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2008: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
KeywordsポリADPリボース / DNA修復 / 活性酸素 / 細胞老化 / 癌化
Research Abstract

Using laser micro-irradiation of living human cell and identification of protein complexes recruited to DNA damaged site by proteomics, we have analyzed and identified DNA damage response of proteins within human cell. For DNA single-strand breaks we have identified two novel human proteins with DNA end-and exo-nuclease activities, which activate poly(ADP-ribose polymerase 1 (PARP1)by creating gap at a nick in DNA. For DNA double-strand breaks (DSB)we identified an ATP-dependent chromatin remodeling complex belonging to ISWI family, CHRAC, which is required for the loading of KU complex at DSB. Especially, ACF1 becomes bound to KU70 more tightly by treatment of cells with chemical agents creating DSB and initiates non-homologous end joining of DSB. Thus, we showed that chromatin remodeling is essential for the initiation of repair of DNA strand breaks.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (33 results)

All 2011 2010 2009 2008 Other

All Journal Article (22 results) (of which Peer Reviewed: 22 results) Presentation (8 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] PALF acts as both a single-stranded DNA end nuclease and a single-stranded DNA 3'-exonuclease and can participate in DNA end joining in a biochemical system2011

    • Author(s)
      Li S, Kanno SI, Watanabe R, Ogiwara H, Kohno T, Watanabe G, Yasui A, and Lieber MR.
    • Journal Title

      J Biol Chem

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The hMsh2-hMsh6 complex acts in concert with monoubiquitinated PCNA and Poll η in response to oxidative DNA damage in human cells2011

    • Author(s)
      Zlatanou A, Despras E, Braz-Petta T, Boubakour-Azzouz I, Pouvelle C, Stewart GS, Nakajima S, Yasui A, Ishchenko AA, Kannouche PL
    • Journal Title

      Mol Cell

      Volume: 43(4) Pages: 649-62

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histone acetylation by p300 at double-strand break sites facilitates SWI/SNF chromatin remodeling and the recruitment of non-homologous end joining factors2011

    • Author(s)
      Ogiwara H, Ui A, Otsuka A, Satoh H, Ymi I, Nakajima S, Yasui A, , Yokota J, and Kohno T
    • Journal Title

      Oncogene

      Volume: 18 Pages: 2135-2146

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutant Cockayne syndrome group B protein inhibits repair of DNA topoisomerase I-DNA covalent complex2011

    • Author(s)
      Horibata K, Saijo M, Bay MN, Lan L, Kuraoka I, Brook PJ, Honma M, Nohmi T, Yasui A., and Tanaka K
    • Journal Title

      Genes Cells

      Volume: 16 Pages: 101-114

    • Related Report
      2010 Annual Research Report 2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] CAMP (C13orf8, ZNF828)is a novel regulator of kinetochore-microtubule attachment2011

    • Author(s)
      Itoh G, Kanno SI, Uchida KS, Chiba S, Sugino S, Watanabe K, Mizuno K, Yasui A, Hirota T, and Tanaka K
    • Journal Title

      EMBO J

      Volume: 30 Pages: 130-144

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment2011

    • Author(s)
      Itoh, et al
    • Journal Title

      EMBO J

      Volume: 30 Pages: 130-144

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The ACF1 complex is required for DNA double-strand break repair in human cells2010

    • Author(s)
      Lan L, Ui A, Nakajima S, Hatakeyama K, Hoshi M, Watanabe R, Janicki S, Ogiwara H, Kohno T, Kanno SI, and Yasui A
    • Journal Title

      Mol Cell

      Volume: 40 Pages: 976-987

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Solution structure of a zinc-finger domain that binds to poly-ADP-ribose2010

    • Author(s)
      Isogai S, Kanno SI, Ariyoshi M, Tochio H, Ito Y, Yasui A, and Shirakawa M
    • Journal Title

      Genes Cells

      Volume: 15 Pages: 101-110

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA polymerase beta-dependent long patch base excision repair in living cells2010

    • Author(s)
      Asagoshi K, Liu Y, Masaoka A, Lan L, Prasad R, Horton JK, Brown AR, Wang XH, Bdour HM, Sobol RW, Taylor JS, Yasui A, and Wilson SH
    • Journal Title

      DNA Repair

      Volume: 9 Pages: 109-119

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Deficiency of the oxidative damage-specific DNA glycosylase NEIL1 leads to reduced germinal center B cell expansion2009

    • Author(s)
      Mori H, Ouchida R, Hijikata A, Kitamura H, Ohara O, Li Y, Gao X, Yasui A, Lloyd RS, and Wang JY
    • Journal Title

      DNA Repair (Amst)

      Volume: 8 Pages: 1328-1332

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA polymerase zeta cooperates with polymerases kappa and iota in translesion DNA synthesis across pyrimidine photodimers in cells from XPV patients2009

    • Author(s)
      Ziv O, Geacintov N, Nakajima S, Yasui A, and Livneh Z
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 106 Pages: 11552-11557

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA polymerase zeta cooperates with polymerases kappa and iota in translesion DNA synthesis across pyrimidine photodimers in cells from XPV patients.2009

    • Author(s)
      Ziv O, Geacintov, N.Nakajima, S, Yasui, A.Livneh, Z.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 106

      Pages: 11552-11557

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deficiency of the oxidative damage-specific DNA glycosylase NEIL1 leads to reduced germinal center B cell expansion.2009

    • Author(s)
      Mori H, et al
    • Journal Title

      DNA Repair 8

      Pages: 1328-1332

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA polymerase beta-dependent long patch base excision repair in living cells.2009

    • Author(s)
      Asagoshi K, et al.
    • Journal Title

      DNA Repair 9

      Pages: 109-119

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku802008

    • Author(s)
      Wei L, Lan L, Hong Z, Yasui A, Ishioka C, and Chiba N
    • Journal Title

      Mol Cell Biol

      Volume: 28 Pages: 7380-7393

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recruitment of mismatch repair proteins to the site of DNA damage in human cells2008

    • Author(s)
      Hong Z, Jiang J, Hashiguchi K, Hoshi M, Lan L, and Yasui A
    • Journal Title

      J. Cell Sci

      Volume: 121 Pages: 3146-3154

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of proliferating cell nuclear antigen ubiquitination in mammalian cells2008

    • Author(s)
      Niimi A, Brown S, Sabbioneda S, Kannouche P, Scott, A, Yasui A, Green CM, and Lehmann AR
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 105 Pages: 16125-16130

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human DNA polymerase iota protects cells against oxidative stress2008

    • Author(s)
      Petta TB, Nakajima S, Zlatanou A, Despras E, Sarasin A, Yasui A, and Kannouche P
    • Journal Title

      EMBO J

      Volume: 27 Pages: 2883-2895

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A polycomb group protein, PHF1, is involved in the response to DNA double-strand breaks in human cell2008

    • Author(s)
      Hong Z, Jiang J, Lan L, Nakajima S, Kanno S, Koseki H, and Yasui A
    • Journal Title

      Nucleic Acids Res

      Volume: 36 Pages: 2937-2947

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recruitment of mismatch repair proteins to the sites of DNA damage in human cells2008

    • Author(s)
      Hong Z., et.al.
    • Journal Title

      J Cell Sci 121

      Pages: 3146-3154

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A polycomb group protein, PHF1, is involved in the response to DNA double-strandf breaks in human cell2008

    • Author(s)
      Hong Z., et.al.
    • Journal Title

      Nucleic Acids Res 36

      Pages: 2939-2947

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with KU802008

    • Author(s)
      Wei L., et.al.
    • Journal Title

      Mol Cell Biol 28

      Pages: 7380-7393

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Roles of chromatin remodeling factors in DNA double-strand break repair in human cell2010

    • Author(s)
      Yasui A
    • Organizer
      The 7^<th> 3R Symposium
    • Place of Presentation
      Toyama Conference Center, Toyama, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] Repair of DNA strand breaks in living human cells and implications for cancer therapy2009

    • Author(s)
      Yasui A, Lan L, Nakajima S, Hatakeyama K, Zehui H, and Kanno SI
    • Organizer
      40^<th> International Symposium of the Princess Takamatsu Cancer Research Fund
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] Mismatch repair proteins at DNA single-and double-strand breaks and UV-lesions2009

    • Author(s)
      Hong Z, and Yasui A.
    • Organizer
      US-EU Conference on Repair of Endogeneous Genome Damage
    • Place of Presentation
      Galveston, Texas, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Spatio-temporal organization of DNA single-strand break repair by PARP, PARG and XRCC1 in human cell2009

    • Author(s)
      Lan L, Nakajima S, Hong S, Kanno SI, and Yasui A.
    • Organizer
      DNA Repair and Mutagenesis, ASM Conference
    • Place of Presentation
      Whistler, BC, Canada
    • Related Report
      2010 Final Research Report
  • [Presentation] Repair of DNA Strand Breaks in Living Human Cell and Its Implication for Cancer Therapy2009

    • Author(s)
      安井明
    • Organizer
      第40回高松宮妃記念国際癌研究シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2009 Annual Research Report
  • [Presentation] Novel AP endonucleases with exonuclease activity and DNA strand break repair in human cell2008

    • Author(s)
      安井明
    • Organizer
      10^<th> International Workshop on Radiation Damage to DNA
    • Place of Presentation
      福島県、裏磐梯ロイヤルホテル
    • Year and Date
      2008-06-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] Novel AP endonuclease with exonuclease activity and DNA strand break repair in human cell2008

    • Author(s)
      Kanno SI, Lan L, Nakajima S, and Yasui A
    • Organizer
      10^<th> International Workshop on Radiation Damage to DNA
    • Place of Presentation
      Urabandai, Fukushima, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] Novel AP endonuclease with 3'-5' exonuclease and single-strand break repair activities in human cell2008

    • Author(s)
      Kanno SI, Sasao S, Kuzuoka H, Suzuki C, Lan L, Nakajima S, and Yasui A.
    • Organizer
      6^<th> 3R Symposium
    • Place of Presentation
      Awajishima Yumebutai, Japan
    • Related Report
      2010 Final Research Report
  • [Book] 分子生物学2011

    • Author(s)
      田沼靖一(編)
    • Publisher
      丸善出版
    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.idac.tohoku.ac.jp/ja/activities/research/Dyn_prot/index.html

    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] UVDE発現による相同組換え頻度向上2009

    • Inventor(s)
      安井明
    • Industrial Property Rights Holder
      安井明
    • Filing Date
      2009-05-22
    • Related Report
      2010 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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