Analysis of human genes that enable high-efficiency gene targeting

• Project/Area Number: 24659035
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Yokohama City University
• Principal Investigator: ADACHI Noritaka 横浜市立大学, 生命ナノシステム科学研究科(八景キャンパス), 教授 (30264675)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ジーンターゲティング / FACS解析 / ジーンターゲティンク

Research Abstract

We have recently constructed an efficient system that enables rapid production of genetically modified human cell lines by gene targeting. Human cell mutants thus made will provide invaluable tools for human medicine and future drug development. In this research project, we have identified several human genes, which, when down-regulated, increase the efficiency of gene targeting by homologous recombination.

Research Products

• [Journal Article] in vivo evidence that phenylalanine 171 acts as a molecular brake for translesion DNA synthesis across benzo[a]pyrene DNA adducts by human DNA polymerase (2014)
  • Author(s): A. Sassa, T. Suzuki, Y. Kanemaru, N. Niimi, H. Fujimoto, A. Katafuchi, P. Gruz, M. Yasui, R.C. Gupta, F. Johnson, T. Ohta, M. Honma, N. Adachi and T. Nohmi
  • Journal Title: DNA Repair Volume: 15 Pages: 21-28
  • DOI: 10.1016/j.dnarep.2013.12.008
  • Peer Reviewed / Open Access
• [Journal Article] Repair of accidental DNA double-strand breaks in the human genome and its relevance to vector DNA integration (2013)
  • Author(s): Adachi N,Saito S,Kurosawa A
  • Journal Title: Gene Technology Volume: 3 Issue: 01
  • DOI: 10.4172/2329-6682.1000e107
• [Journal Article] C-terminal region of DNA ligase IV drives XRCC4/DNA ligase IV complex to chromatin (2013)
  • Author(s): Liu S, Liu X, Kamdar RP, Wanotayan R, Sharma MK, Adachi N, Matsumoto Y
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 439 Issue: 2 Pages: 173-178
  • DOI: 10.1016/j.bbrc.2013.08.068
  • Peer Reviewed
• [Journal Article] Endogenous factors causative of spontaneous DNA damage that leads to random integration in human cells. (2013)
  • Author(s): N. Adachi et al.
  • Journal Title: Gene Technology Volume: 2 Issue: 01 Pages: 105-105
  • DOI: 10.4172/2329-6682.1000105
  • Peer Reviewed
• [Journal Article] Generation and use of genetically modified human cell lines : a promising approach for in vitro toxicology studies (2013)
  • Author(s): Adachi N
  • Journal Title: J Clinic Toxicol Volume: 3(5) Issue: 05 Pages: 45-45
  • DOI: 10.4172/2161-0495.s1.009
• [Journal Article] DNA Ligase IV and Artemis Act Cooperatively to Suppress Homologous Recombination in Human Cells: Implications for DNA Double-Strand Break Repair. (2013)
  • Author(s): Kurosawa A, Saito S, So S, Hashimoto M, Iwabuchi K, Watabe H, Adachi N.
  • Journal Title: PLoS One Volume: 8 Issue: 8 Pages: e72253-e72253
  • DOI: 10.1371/journal.pone.0072253
  • Peer Reviewed
• [Journal Article] Restoration of mismatch repair functions in human cell line Nalm-6, which has high efficiency for gene targeting (2013)
  • Author(s): T. Suzuki, A. Ukai, M. Honma, N. Adachi and T. Nohmi
  • Journal Title: PLoS.One Volume: 8 Issue: 4 Pages: e61189-e61189
  • DOI: 10.1371/journal.pone.0061189
  • Peer Reviewed
• [Journal Article] Interference in DNA replieation can cause mitotic chromosomal breakage unassociated with double-strand breaks (2013)
  • Author(s): Fujita Mari, Sasanuma H, Kimiyo N. Yamamoto Harada H, Kurosawa A, Adachi N, Omura M, Hiraoka M, Takeda S, Hirota K.
  • Journal Title: PLos One Volume: 8 Issue: 4 Pages: 60043-60043
  • DOI: 10.1371/journal.pone.0060043
  • Peer Reviewed
• [Journal Article] Both CpG methylation and AID are required for the fragility of the human Bcl-2 major breakpoint region : Implications for the timing of the breaks in the t(l4;l8) (2013)
  • Author(s): Cui X,Lu Z,Kurosawa A,Klemm L,Bagshaw A,Tsai A,Gemmell N,Muschen M,Adachi N,Hsieh CL,Lieber MR
  • Journal Title: Mol Cell Biol Volume: 33(5) Issue: 5 Pages: 947-57
  • DOI: 10.1128/mcb.01436-12
• [Journal Article] Restoration of mismatch repair functions in human cell line Nalm-6, which has high efficiency for gene targeting. (2013)
  • Author(s): Adachi N. et al.
  • Journal Title: PLoS ONE Volume: 8
  • Peer Reviewed
• [Journal Article] Model for MLL translocations in therapy-related leukemia involving topoisomerase IIbeta mediated DNA strand breaks and gene proximity (2012)
  • Author(s): Cowell IG,Sondka Z,Smith K,Lee KC,Manville CM,Sidorczuk-Lesthuruge M,Rance HA,Padget K,]ackson GH,Adachi N,Austin CA
  • Journal Title: Proc Natl Acad Sci U S A Volume: 109(23) Issue: 23 Pages: 8989-94
  • DOI: 10.1073/pnas.1204406109
• [Journal Article] Artemis C-terminal region facilitates efficient V(D)J recombination through its interaction with both DNA Ligase IV and DNA-PKcs. (2012)
  • Author(s): N. Adachi, et al.
  • Journal Title: J.Exp. Med. Volume: 209 Issue: 5 Pages: 955-963
  • DOI: 10.1084/jem.20111437
  • Peer Reviewed
• [Journal Article] The helicase domain and C-terminus of human RecQL4 facilitate replication elongation on DNA templates damaged by ionizing radiation. (2012)
  • Author(s): Kohzaki M
  • Journal Title: Carcinogenesis Volume: 33 Issue: 6 Pages: 1203-1210
  • DOI: 10.1093/carcin/bgs149
  • Peer Reviewed
• [Journal Article] Model for MLL translocations in therapy-related leukemia involving topoisomerase IIbeta mediated DNA strand breaks and gene proximity. (2012)
  • Author(s): Adachi N. et al.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 109 Pages: 8989-8994
  • Peer Reviewed
• [Remarks]
  • URL: http://dnar.sci.yokohama-cu.ac.jp/
• [Patent(Industrial Property Rights)] 遺伝子ターゲティングベクター及びその利用方法 (2012)
  • Inventor(s): 足立典隆
  • Industrial Property Rights Holder: 足立典隆
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-12-12
  • Overseas
• [Patent(Industrial Property Rights)] 遺伝子ターゲティングベクター、その作製方法及び利用方法 (2012)
  • Inventor(s): 足立典隆
  • Industrial Property Rights Holder: 足立典隆
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-05-24
  • Overseas