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

• Project/Area Number: 20241011
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Tohoku 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: ¥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.

Research Products

• [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 system (2011)
  • Author(s): Li S, Kanno SI, Watanabe R, Ogiwara H, Kohno T, Watanabe G, Yasui A, and Lieber MR.
  • Journal Title: J Biol Chem
  • 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 cells (2011)
  • 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
  • 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 factors (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Mutant Cockayne syndrome group B protein inhibits repair of DNA topoisomerase I-DNA covalent complex (2011)
  • 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
  • Peer Reviewed
• [Journal Article] CAMP (C13orf8, ZNF828)is a novel regulator of kinetochore-microtubule attachment (2011)
  • 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
  • Peer Reviewed
• [Journal Article] CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment (2011)
  • Author(s): Itoh, et al
  • Journal Title: EMBO J Volume: 30 Pages: 130-144
  • Peer Reviewed
• [Journal Article] The ACF1 complex is required for DNA double-strand break repair in human cells (2010)
  • 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
  • Peer Reviewed
• [Journal Article] Solution structure of a zinc-finger domain that binds to poly-ADP-ribose (2010)
  • 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
  • Peer Reviewed
• [Journal Article] DNA polymerase beta-dependent long patch base excision repair in living cells (2010)
  • 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
  • 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, 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
  • 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, and Livneh Z
  • Journal Title: Proc Natl Acad Sci USA Volume: 106 Pages: 11552-11557
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80 (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Recruitment of mismatch repair proteins to the site of DNA damage in human cells (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Regulation of proliferating cell nuclear antigen ubiquitination in mammalian cells (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Human DNA polymerase iota protects cells against oxidative stress (2008)
  • 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
  • Peer Reviewed
• [Journal Article] A polycomb group protein, PHF1, is involved in the response to DNA double-strand breaks in human cell (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Recruitment of mismatch repair proteins to the sites of DNA damage in human cells (2008)
  • Author(s): Hong Z., et.al.
  • Journal Title: J Cell Sci 121 Pages: 3146-3154
  • Peer Reviewed
• [Journal Article] A polycomb group protein, PHF1, is involved in the response to DNA double-strandf breaks in human cell (2008)
  • Author(s): Hong Z., et.al.
  • Journal Title: Nucleic Acids Res 36 Pages: 2939-2947
  • Peer Reviewed
• [Journal Article] Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with KU80 (2008)
  • Author(s): Wei L., et.al.
  • Journal Title: Mol Cell Biol 28 Pages: 7380-7393
  • Peer Reviewed
• [Presentation] Roles of chromatin remodeling factors in DNA double-strand break repair in human cell (2010)
  • Author(s): Yasui A
  • Organizer: The 7^<th> 3R Symposium
  • Place of Presentation: Toyama Conference Center, Toyama, Japan
• [Presentation] Repair of DNA strand breaks in living human cells and implications for cancer therapy (2009)
  • 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
• [Presentation] Mismatch repair proteins at DNA single-and double-strand breaks and UV-lesions (2009)
  • Author(s): Hong Z, and Yasui A.
  • Organizer: US-EU Conference on Repair of Endogeneous Genome Damage
  • Place of Presentation: Galveston, Texas, USA
• [Presentation] Spatio-temporal organization of DNA single-strand break repair by PARP, PARG and XRCC1 in human cell (2009)
  • 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
• [Presentation] Repair of DNA Strand Breaks in Living Human Cell and Its Implication for Cancer Therapy (2009)
  • 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
• [Presentation] Novel AP endonucleases with exonuclease activity and DNA strand break repair in human cell (2008)
  • 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
• [Presentation] Novel AP endonuclease with exonuclease activity and DNA strand break repair in human cell (2008)
  • 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
• [Presentation] Novel AP endonuclease with 3'-5' exonuclease and single-strand break repair activities in human cell (2008)
  • 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
• [Book] 分子生物学 (2011)
  • Author(s): 田沼靖一(編)
  • Publisher: 丸善出版
• [Remarks]
  • URL: http://www.idac.tohoku.ac.jp/ja/activities/research/Dyn_prot/index.html
• [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