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Topoisomerase I inhibition and peripheral nerve injury induce DNA breaks and ATF3-associated axon regeneration in sensory neurons.
Cheng, Yung-Chih; Snavely, Andrew; Barrett, Lee B; Zhang, Xuefei; Herman, Crystal; Frost, Devlin J; Riva, Priscilla; Tochitsky, Ivan; Kawaguchi, Riki; Singh, Bhagat; Ivanis, Jelena; Huebner, Eric A; Arvanites, Anthony; Oza, Vatsal; Davidow, Lance; Maeda, Rie; Sakuma, Miyuki; Grantham, Alyssa; Wang, Qing; Chang, Amelia N; Pfaff, Kathleen; Costigan, Michael; Coppola, Giovanni; Rubin, Lee L; Schwer, Bjoern; Alt, Frederick W; Woolf, Clifford J.
Affiliation
  • Cheng YC; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Snavely A; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Barrett LB; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Zhang X; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Herman C; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA.
  • Frost DJ; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA.
  • Riva P; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA.
  • Tochitsky I; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Kawaguchi R; Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Singh B; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Ivanis J; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA.
  • Huebner EA; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Arvanites A; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Oza V; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Davidow L; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Maeda R; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA.
  • Sakuma M; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Grantham A; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA.
  • Wang Q; Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Chang AN; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Pfaff K; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Costigan M; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Anaesthesia Department, Boston Children's Hospital, Boston, MA 02115, USA.
  • Coppola G; Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Rubin LL; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Schwer B; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Alt FW; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Woolf CJ; F.M. Kirby Neurobiology Center, Program in Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address: clifford.woolf@childre
Cell Rep ; 36(10): 109666, 2021 09 07.
Article in En | MEDLINE | ID: mdl-34496254
ABSTRACT
Although axonal damage induces rapid changes in gene expression in primary sensory neurons, it remains unclear how this process is initiated. The transcription factor ATF3, one of the earliest genes responding to nerve injury, regulates expression of downstream genes that enable axon regeneration. By exploiting ATF3 reporter systems, we identify topoisomerase inhibitors as ATF3 inducers, including camptothecin. Camptothecin increases ATF3 expression and promotes neurite outgrowth in sensory neurons in vitro and enhances axonal regeneration after sciatic nerve crush in vivo. Given the action of topoisomerases in producing DNA breaks, we determine that they do occur immediately after nerve damage at the ATF3 gene locus in injured sensory neurons and are further increased after camptothecin exposure. Formation of DNA breaks in injured sensory neurons and enhancement of it pharmacologically may contribute to the initiation of those transcriptional changes required for peripheral nerve regeneration.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sensory Receptor Cells / Axons / DNA Topoisomerases, Type I / Activating Transcription Factor 3 / DNA Breaks / Peripheral Nerve Injuries Type of study: Prognostic_studies / Risk_factors_studies Limits: Animals Language: En Journal: Cell Rep Year: 2021 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sensory Receptor Cells / Axons / DNA Topoisomerases, Type I / Activating Transcription Factor 3 / DNA Breaks / Peripheral Nerve Injuries Type of study: Prognostic_studies / Risk_factors_studies Limits: Animals Language: En Journal: Cell Rep Year: 2021 Document type: Article Affiliation country: