Characterization of the novel human AP endonuclease and poly-ADP-ribosyl transferase.

• Project/Area Number: 23510059
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Tohoku University
• Principal Investigator: KANNO Shin-ichiro 東北大学, 加齢医学研究所, 講師 (10400417)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: DNA修復 / APエンドヌクレアーゼ / PARP1 / ポリADPリボシル化 / アセチルトランスフェラーゼ

Research Abstract

The CYR motif was first identified in the repair protein, PALF (ALPF), and found in various proteins of DNA metabolism and DNA repair. We newly identified the CYR motif containing proteins, Drosophila CG1218 and its human ortholog C4orf27, which contained a conserved DUF2228 domain. We hypothesized that these proteins have DNA metabolism related functions. We isolated cDNA of CG1218 and human C4orf27, and characterized these proteins. Here we show that; 1) a CG1218 protein accumulates at DNA damaged site and human C4orf27 protein forms a hetero dimmer with PARP1 and accumulates at DNA damaged site 2) CG1218 and C4orf27 possess endo/exonuclease activities against abasic site. 3) Suppression of the expression of C4orf27 using siRNA provided the cells with sensitivity to MMS, which produces methylated bases leading to single-strand breaks. These data suggest that DUF2228 protein CG1218-PA and C4orf27 play important roles in the repair of DNA base damage and single-strand breaks.

Research Products

• [Journal Article] The BRCA1/BARD1-interacting protein OLA1 functions in centrosome regulation. (2014)
  • Author(s): Matsuzawa A, Kanno S, Nakayama M, Mochiduki H, Wei L, Shimaoka T, Furukawa Y, Kato K, Shibata S, Yasui A, Ishioka C, Chiba N.
  • Journal Title: Mol Cell Volume: 53 Issue: 1 Pages: 101-114
  • DOI: 10.1016/j.molcel.2013.10.028
  • Peer Reviewed / Open Access
• [Journal Article] Possible involvement of LKB1-AMPK signaling in non-homologous end joining. (2014)
  • Author(s): Ui A, Ogiwara H, Nakajima S, Kanno S-I, Watanabe R, Harata M, Okayama H, Harris CC, Yokota J, Yasui A and Kohno T
  • Journal Title: Oncogene Volume: 33 Issue: 13 Pages: 1640-1648
  • DOI: 10.1038/onc.2013.125
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Damage response of XRCC1 at sites of DNA single strand breaks is regulated by phosphorylation and ubiquitination after degradation of poly (ADP) ribose. (2013)
  • Author(s): Leizhen Wei,Satoshi Nakajima, Ching-Lung Hsieh, Shinichiro Kanno, Mitsuko Masutani, Arthur S. Levine1, Akira Yasui, Li Lan
  • Journal Title: J Cell Sci. Volume: 126(Pt 19) Issue: 19 Pages: 4414-23
  • DOI: 10.1242/jcs.128272
  • Peer Reviewed
• [Journal Article] Furry promotes acetylation of microtubules in the mitotic spindle via inhibition of SIRT2 tubulin-deacetylase (2013)
  • Author(s): Tomoaki Nagai, Masanori Ikeda, Shuhei Chiba, Shin-ichiro Kanno and Kensaku Mizuno
  • Journal Title: J Cell Sci Volume: 126 Issue: 19 Pages: 4369-80
  • DOI: 10.1242/jcs.127209
  • Peer Reviewed
• [Journal Article] The nucleoporin Nup188 is required for chromosome alignment in mitosis (2013)
  • Author(s): 伊藤剛、杉野史朗、池田真教、水口万裕美、菅野新一郎、M.A.Amin、家村顕自、安井明、広田亨、田中耕三
  • Journal Title: Cancer Science Volume: (in press) Issue: 7 Pages: 871-879
  • DOI: 10.1111/cas.12159
  • Peer Reviewed
• [Journal Article] Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair (2012)
  • Author(s): X. Zhang
  • Journal Title: Nat.Genet Volume: 44 Issue: 5 Pages: 593-597
  • DOI: 10.1038/ng.2228
  • Peer Reviewed
• [Journal Article] WRNIP1 accumulates at laser light irradiated sites rapidly via its ubiquitin-binding zinc finger domain and independently from its ATPase domain. (2012)
  • Author(s): Nomura, H., Yoshimura, A., Edo, T., Kanno, S.I., Tada, S., Seki, M., Yasui, A., and Enomoto, T.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 417 Issue: 4 Pages: 1145-1150
  • DOI: 10.1016/j.bbrc.2011.12.080
  • Peer Reviewed
• [Journal Article] PALF acts as both a single-stranded DNA endonuclease and a single-stranded DNA 3'-exonuclease and can participate in DNA end joining in abiochemical system (2011)
  • Author(s): Li S, et al
  • Journal Title: J Biol Chem Volume: 286 Issue: 42 Pages: 36368-36377
  • DOI: 10.1074/jbc.m111.287797
  • Peer Reviewed
• [Journal Article] CAMP (C13orf8, ZNF828)is a novel regulator of kinetochore-microtubule attachment. (2011)
  • Author(s): Itoh, G, Kanno, S, Uchida, K, S, K, Chiba, S, Sugino, S, Watanabe, K, Mizuno, K, Yasui, A, Hirota, T, and Tanaka, K.
  • Journal Title: EMBO J Volume: 30(1) Issue: 1 Pages: 130-44
  • DOI: 10.1038/emboj.2010.276
  • Peer Reviewed
• [Journal Article] PALF acts as both a single-stranded DNA endonuclease 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. Volume: 286(42) Pages: 36368-36377
  • Peer Reviewed
• [Presentation] Chromatin remodeling factors required for the repair of DNA double-strand breaks and their absence in cancer cells (2012)
  • Author(s): Reiko Watanabe, Ayako Ui, Shin-ichiro Kanno, Hideaki Ogiwara, Takahiro Nagase, Takashi Kohno, and Akira Yasui
  • Organizer: 日本分子生物学会
  • Place of Presentation: 福岡国際会議場マリンメッセ福岡
• [Remarks] 東北大学加齢医学研究所ホームページ
  • URL: http://www.idac.tohoku.ac.jp/ja/activities/research/Dyn_prot/index.html