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TRF2-Mediated Control of Telomere DNA Topology as a Mechanism for Chromosome-End Protection.

  • Benarroch-Popivker D Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France.
  • Pisano S Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France.
  • Mendez-Bermudez A Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France; International Laboratory in Hematology and Cancer, Shanghai Jiao Tong University School of Medicine/Ruijin Hospital/CNRS/INSERM/Nice University, Pôle Sino-Français de Recherche en Sciences du Vivant et Génomique, Shanghai Ruijin Hospital, Huangpu, Shanghai 200025, P.R. China.
  • Lototska L Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France.
  • Kaur P Physics Department, North Carolina State University at Raleigh, Raleigh, NC 27695, USA.
  • Bauwens S Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France.
  • Djerbi N Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France.
  • Latrick CM Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France.
  • Fraisier V Cell and Tissue Imaging Platform (PICT-IBiSA), Nikon Imaging Centre, UMR 144 CNRS Institut Curie, 75248 Paris Cedex 05, France.
  • Pei B Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France.
  • Gay A Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France.
  • Jaune E Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France.
  • Foucher K Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France.
  • Cherfils-Vicini J Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France.
  • Aeby E Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
  • Miron S Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Bâtiment 144, CEA Saclay, Gif-sur-Yvette F-91191, France.
  • Londoño-Vallejo A UMR3244, Telomeres and Cancer Laboratory, Institut Curie, Paris 75248, France.
  • Ye J International Laboratory in Hematology and Cancer, Shanghai Jiao Tong University School of Medicine/Ruijin Hospital/CNRS/INSERM/Nice University, Pôle Sino-Français de Recherche en Sciences du Vivant et Génomique, Shanghai Ruijin Hospital, Huangpu, Shanghai 200025, P.R. China.
  • Le Du MH Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Bâtiment 144, CEA Saclay, Gif-sur-Yvette F-91191, France.
  • Wang H Physics Department, North Carolina State University at Raleigh, Raleigh, NC 27695, USA.
  • Gilson E Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France; International Laboratory in Hematology and Cancer, Shanghai Jiao Tong University School of Medicine/Ruijin Hospital/CNRS/INSERM/Nice University, Pôle Sino-Français de Recherche en Sciences du Vivant et Génomique, Shanghai Ruijin Hospital, Huangpu, Shanghai 200025, P.R. China; Department of Genetics, CHU Nice, Nice 06202, France. Electronic address: eric.gilson@unice.fr.
  • Giraud-Panis MJ Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France. Electronic address: giraud-panis@unice.fr.
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  • 2016-01-18
Published in:
  • Molecular cell. - 2016
DNA topology
DNA wrapping
RAP1
TRF2
telomere
Ataxia Telangiectasia Mutated Proteins
Base Pairing
DNA
DNA Damage
DNA End-Joining Repair
HeLa Cells
Humans
Lysine
Models, Molecular
Mutation
Nucleic Acid Conformation
Protein Structure, Tertiary
Signal Transduction
Telomere
Telomere-Binding Proteins
Telomeric Repeat Binding Protein 2
English The shelterin proteins protect telomeres against activation of the DNA damage checkpoints and recombinational repair. We show here that a dimer of the shelterin subunit TRF2 wraps ∼ 90 bp of DNA through several lysine and arginine residues localized around its homodimerization domain. The expression of a wrapping-deficient TRF2 mutant, named Top-less, alters telomeric DNA topology, decreases the number of terminal loops (t-loops), and triggers the ATM checkpoint, while still protecting telomeres against non-homologous end joining (NHEJ). In Top-less cells, the protection against NHEJ is alleviated if the expression of the TRF2-interacting protein RAP1 is reduced. We conclude that a distinctive topological state of telomeric DNA, controlled by the TRF2-dependent DNA wrapping and linked to t-loop formation, inhibits both ATM activation and NHEJ. The presence of RAP1 at telomeres appears as a backup mechanism to prevent NHEJ when topology-mediated telomere protection is impaired.
Language
  • English
Open access status
bronze
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Persistent URL
https://sonar.ch/global/documents/162910
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