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

2013 Fiscal Year Final Research Report

• 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
• Keywords: DNA修復 / APエンドヌクレアーゼ

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, and Chiba N
  • Journal Title: Molecular Cell Volume: 53(1) Pages: 101-14
  • DOI: 10.1016/j.molcel.2013.10.028
  • Peer Reviewed
• [Journal Article] Li Lan 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. Levine, Akira Yasui
  • Journal Title: J. Cell Sci Volume: 126(Pt 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 Pages: 4369-80
  • DOI: 10.1242/jcs.127209
  • Peer Reviewed
• [Journal Article] Nucleoporin Nup188 is required for chromosome alignment in mitosis (2013)
  • Author(s): Go Itoh, Shiro Sugino, Masanori Ikeda, Mayumi Mizuguchi, Shin-ichiro Kanno, Mohammed A. Amin, Kenji Iemura, Akira Yasui, Toru Hirota and Kozo Tanaka
  • Journal Title: Cancer Sci Volume: 104(7) Pages: 871-9
  • 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): Zhang X, Horibata K, Saijo M, Ishigami C, Ukai A, Kanno S, Tahara H, Neilan EG, Honma M, Nohmi T, Yasui A, Tanaka K
  • Journal Title: Nat Genet Volume: 44(5) Pages: 593-7
  • 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, Tada S, Seki M, Yasui A, Enomoto T
  • Journal Title: Biochem Biophys Res Commun Volume: 417(4) Pages: 1145-50
  • DOI: 10.1016/j.bbrc.2011.12.080
  • Peer Reviewed
• [Journal Article] Polynucleotide kinase and aprataxin-like forkhead -associated protein (PALF) acts as both a singlestranded 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 S, Watanabe R, Ogiwara H, Kohno T, Watanabe G, Yasui A, Lieber MR
  • Journal Title: J Biol Chem Volume: 286(42) Pages: 36368-77
  • DOI: 10.1074/jbc.M111.287797
  • Peer Reviewed
• [Journal Article] CAMP(C13orf8, ZNF828) is anovel 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) Pages: 130-44
  • DOI: 10.1038/emboj.2010.276
  • Peer Reviewed
• [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