GeneticanalysisofDNAstrandbreakrepairinhumancelIs

• Project/Area Number: 21590066
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• 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, 教授 (30264675)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 遺伝子ノックアウト / DNA鎖切断 / エンドジョイニング / 組換え / NDA鎖切断

Research Abstract

In this study, we have generated a series of human cell mutants that lack one or two genes implicated in DNA strand break repair. These gene-knockout mutants allowed us to perform comprehensive geneticanalysis of human DNA repair genes, especially those involved in DNA double-strand break repair and genetic recombination.

Research Products

• [Journal Article] EDGF/pisindependent HIV-l repli cation demonstrates a role for HRP-2 and remains sensitive to inhibition by LEDGINs (2012)
  • Author(s): Schrijvers R, De Rijck J, Demeu lemeester J, Adachi N, Vets S, Ronen K, Christ F, Bushman FD, Debyser Z, Gt jsbers R.
  • Journal Title: PLoS Pathog Volume: 8 Pages: 1002558-1002558
• [Journal Article] Nucleofection-based gene targeting in human pie-B cells (2012)
  • Author(s): Kurosawa A, Saito S, Mort M, Adachi N.
  • Journal Title: Gene Volume: 492 Pages: 305-308
• [Journal Article] Impaired cell adhesion, apoptosis, and signaling in WASP genedisrupted Nalm-6 pie-B cells and recovery of cell adhesion using a transducible form of WASp (2012)
  • Author(s): Sate R, Iiizumi S, Kim ES, Honda F, Lee SK, Adachi N, Koyama H, Mizutani S, Morie T.
  • Journal Title: Int J Hematol Volume: 95 Pages: 299-310
• [Journal Article] The helicase domain and C-terminus of human RecQL4 facilitate replication elongation on DNA templates damaged by ionizing radiation (2012)
  • Author(s): Adachi N., et al
  • Journal Title: Carcinogenesis Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Nucleofection-based gene targeting in human pre-B cells (2012)
  • Author(s): Kurosawa A, Adachi N
  • Journal Title: Gene Volume: 492 Pages: 305-308
  • Peer Reviewed
• [Journal Article] LEDGF/p75-independent HIV-1 replication demonstrates a role for HRP-2 and remains sensitive to inhibition by LEDGINs (2012)
  • Author(s): Adachi N., et al
  • Journal Title: PLoS Pathogens Volume: 8
  • Peer Reviewed
• [Journal Article] Highefficiency gene tar geting in a human pie-B cell line : towards the human gene knockout project (2010)
  • Author(s): Adachi N.
  • Journal Title: Genome Biol Volume: 11 Pages: 1-1
• [Journal Article] Functions and regulation of Artemis : A goddess in the maintenance of genome integrity (2010)
  • Author(s): Kurosawa A, Adachi N.
  • Journal Title: J Radiat Res Volume: 51 Pages: 503-509
  • NAID: 10026644156
• [Journal Article] OGFODl, a member of the 2oxoglutarate and iron dependent dioxygenase family, functions in ischemic signaling (2010)
  • Author(s): Saito K, Adachi N, Koyama H, Matsushita M.
  • Journal Title: FEBS Left Volume: 584 Pages: 3340-3347
• [Journal Article] Chromosomal manipulation by sitespecific recombinases and fluore scent protein-based vectors (2010)
  • Author(s): Uemura M, Niwa Y, Kakazu N, Adachi N, Kinoshita K.
  • Journal Title: PLoS ONE Volume: 5 Pages: 9846-9846
• [Journal Article] FENl functions in long patch base excision repair under conditions of oxidative stress in vertebrate cells (2010)
  • Author(s): Asagoshi K, Tana K, Chastain PD II, Adachi N, Sonoda E, Kikuchi K, Koyama H, NagataK, Kaufman DG, Takeda S, Wilson SH, Watanabe M, Swenberg JA, Nakamura J.
  • Journal Title: Mol Cancer Res Volume: 8 Pages: 204-215
• [Journal Article] Functions and regulation of Artemis : A goddess in the maintenance of genome integrity. (2010)
  • Author(s): Kurosawa A, Adachi N.
  • Journal Title: J.Radiat.Res. Volume: 51 Pages: 503-509
  • NAID: 10026644156
  • Peer Reviewed
• [Journal Article] OGFOD1, a member of the 2-oxoglutarate and iron dependent dioxygenase family, functions in ischemic signaling. (2010)
  • Author(s): Saito K., et al.
  • Journal Title: FEBS Lett. Volume: 584 Pages: 3340-3347
  • Peer Reviewed
• [Journal Article] Chromosomal manipulation by site-specific recombinases and fluorescent protein-based vectors (2010)
  • Author(s): Adachi, N., et al.
  • Journal Title: PLoS ONE 5
  • Peer Reviewed
• [Journal Article] FEN1 functions in long patch base excision repair under conditions of oxidative stress in vertebrate cells (2010)
  • Author(s): Adachi, N., et al.
  • Journal Title: Mol.Cancer Res. 8 Pages: 204-215
  • Peer Reviewed
• [Journal Article] Functions and regulation of Artemis : A goddess in the maintenance of genome integrity (2010)
  • Author(s): Kurosawa, A., Adachi, N.
  • Journal Title: J.Radiat.Res. 51(印刷中)
  • NAID: 10026644156
  • Peer Reviewed
• [Journal Article] The iron chelator Dp44mT causes DNA damage and selective inhibition of topoisomer ase-Ilalpha in breast cancer cells (2009)
  • Author(s): Rae VA, Klein SR, Agama KK, Toyoda E, Adachi N, Pommier YG, Shacter EB.
  • Journal Title: Cancer Res Volume: 69 Pages: 948-957
• [Journal Article] Loss of Bloom syndrome protein destabilizes human gene cluster architecture (2009)
  • Author(s): Killen MW, Stults DM, Adachi N, Hanakahi L, Pierce AJ.
  • Journal Title: Hum Mol Genet Volume: 18 Pages: 3417-3428
• [Journal Article] Genetic evidence that the nonhomologous endjoining repair pathway is involved in LINE retro transposition (2009)
  • Author(s): Suzuki J, Yamaguchi K, Kajikawa M, Ichiyanagi K, Adachi N, Koyama H, Takeda S, Okada N.
  • Journal Title: PLoS Genetics Volume: 5 Pages: 1000461-1000461
• [Journal Article] Topoisomerase Ilalpha inhib ition following DNA transfection greatly enhances random integration in a human pie-B lymphocyte cell line (2009)
  • Author(s): Toyoda E, Kurosawa A, Kamekawa H, Adachi N.
  • Journal Title: Biochem Biophys Res Commun Volume: 382 Pages: 492-496
• [Journal Article] Heterozygous disruption of the DNA topoisomerase I gene confers cellular resistance to camptothecin in human cells (2009)
  • Author(s): Toyoda E, Kurosawa A, Fu j i i M, Adachi N.
  • Journal Title: Biol Pharm Bull Volume: 32 Pages: 724-727
  • NAID: 110007160669
• [Journal Article] Molecular mechanism of protein assembly on DNA double strand breaks in the nonhomologous endjoining pathway (2009)
  • Author(s): Yano K, Morotomi-Yano K, Adachi N, Akiyama H.
  • Journal Title: J Radiat Res Volume: 50 Pages: 97-108
  • NAID: 10025911271
• [Journal Article] Model for MLL translocations in therapyrelated leukemia involving topoisomerase Ilbeta mediated DNA strand breaks and gene proximity
  • Author(s): DCowell IG, Sondka Z, Smith K, Lee KC, Manville CM, SidorczukLesthuruge M, Rance HA, Padget K, Jackson GH, Adachi N, Austin CA.
  • Journal Title: Proc Natl Acad Sci USA Volume: (in press)
• [Journal Article] The helicase domain and Cterminus of human RecQL4 facilitate replication elongation on DNA templates damaged by ionizing radiation
  • Author(s): Kohzaki M, Chiourea M, Versini G, Adachi N, Takeda S, Gages S, Halazonetis TD.
  • Journal Title: Carcinogenesis Volume: (in press)
• [Journal Article] Artemis Cterminal region facilitates efficient V(D) J recombination through its interaction with both DNA Ligase IV and DNA-PKcs
  • Author(s): Malu S, De loannes P, Kozlov M, Greene M, Francis, D, Hanna M, Pena, J, Escalante CR, Kurosawa A, ErdjumentBromage H, Tempst P, Adachi N, Vezzoni P, Villa A, Aggarwal AK, Certes P.
  • Journal Title: J Exp Med Volume: (in press)
• [Remarks]
  • URL: http://dnar.sci.yokohama-cu.ac.jp/