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Modular antibodies reveal DNA damage-induced mono-ADP-ribosylation as a second wave of PARP1 signaling.
Longarini, Edoardo José; Dauben, Helen; Locatelli, Carolina; Wondisford, Anne R; Smith, Rebecca; Muench, Charlotte; Kolvenbach, Andreas; Lynskey, Michelle Lee; Pope, Alexis; Bonfiglio, Juan José; Jurado, Eva Pinto; Fajka-Boja, Roberta; Colby, Thomas; Schuller, Marion; Ahel, Ivan; Timinszky, Gyula; O'Sullivan, Roderick J; Huet, Sébastien; Matic, Ivan.
Afiliação
  • Longarini EJ; Research Group of Proteomics and ADP-Ribosylation Signaling, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
  • Dauben H; Research Group of Proteomics and ADP-Ribosylation Signaling, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
  • Locatelli C; Research Group of Proteomics and ADP-Ribosylation Signaling, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
  • Wondisford AR; Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
  • Smith R; Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, BIOSIT (Biologie, Santé, Innovation Technologique de Rennes) - UMS 3480, US 018, 35000 Rennes, France.
  • Muench C; Research Group of Proteomics and ADP-Ribosylation Signaling, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
  • Kolvenbach A; Research Group of Proteomics and ADP-Ribosylation Signaling, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
  • Lynskey ML; Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
  • Pope A; Research Group of Proteomics and ADP-Ribosylation Signaling, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
  • Bonfiglio JJ; Research Group of Proteomics and ADP-Ribosylation Signaling, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
  • Jurado EP; Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, BIOSIT (Biologie, Santé, Innovation Technologique de Rennes) - UMS 3480, US 018, 35000 Rennes, France; Laboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, Biological Research Centre, Eötvös Lorán
  • Fajka-Boja R; Laboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, Biological Research Centre, Eötvös Loránd Research Network (ELKH), 6276 Szeged, Hungary; Department of Immunology, Albert Szent-Györgyi Medical School, Faculty of Science and Informatics, University of Szeged, 6720 Szeged, Hungary
  • Colby T; Research Group of Proteomics and ADP-Ribosylation Signaling, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
  • Schuller M; Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
  • Ahel I; Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
  • Timinszky G; Laboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, Biological Research Centre, Eötvös Loránd Research Network (ELKH), 6276 Szeged, Hungary.
  • O'Sullivan RJ; Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
  • Huet S; Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, BIOSIT (Biologie, Santé, Innovation Technologique de Rennes) - UMS 3480, US 018, 35000 Rennes, France; Institut Universitaire de France, Paris, France. Electronic address: sebastien.huet@univ-rennes.fr.
  • Matic I; Research Group of Proteomics and ADP-Ribosylation Signaling, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany; Cologne Excellence Cluster for Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany. Electronic address: imatic@age.mpg.de
Mol Cell ; 83(10): 1743-1760.e11, 2023 05 18.
Article em En | MEDLINE | ID: mdl-37116497
ABSTRACT
PARP1, an established anti-cancer target that regulates many cellular pathways, including DNA repair signaling, has been intensely studied for decades as a poly(ADP-ribosyl)transferase. Although recent studies have revealed the prevalence of mono-ADP-ribosylation upon DNA damage, it was unknown whether this signal plays an active role in the cell or is just a byproduct of poly-ADP-ribosylation. By engineering SpyTag-based modular antibodies for sensitive and flexible detection of mono-ADP-ribosylation, including fluorescence-based sensors for live-cell imaging, we demonstrate that serine mono-ADP-ribosylation constitutes a second wave of PARP1 signaling shaped by the cellular HPF1/PARP1 ratio. Multilevel chromatin proteomics reveals histone mono-ADP-ribosylation readers, including RNF114, a ubiquitin ligase recruited to DNA lesions through a zinc-finger domain, modulating the DNA damage response and telomere maintenance. Our work provides a technological framework for illuminating ADP-ribosylation in a wide range of applications and biological contexts and establishes mono-ADP-ribosylation by HPF1/PARP1 as an important information carrier for cell signaling.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Histonas / ADP-Ribosilação Tipo de estudo: Risk_factors_studies Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Alemanha
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Histonas / ADP-Ribosilação Tipo de estudo: Risk_factors_studies Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Alemanha