Regulation of ALT-associated homology-directed repair by polyADP-ribosylation
| Autor: | Ian D. Waddell, Robert W. Sobol, Kate M. Smith, Justin L. Roncaioli, Felipe da Veiga Leprevost, Song My Hoang, Dattatreya Mellacharevu, Dominique Ray-Gallet, Michelle L. Lynskey, Roderick J. O’Sullivan, Ragini Bhargava, Jonathan Barroso-González, Nicole Kaminski, Geneviève Almouzni, Anne R. Wondisford, Jianfeng Li, Donald J. Ogilvie, Alexey I. Nesvizhskii, Dominic I. James, Callen T. Wallace, Simon C. Watkins, Laura García-Expósito |
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| Přispěvatelé: | University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Manchester [Manchester], University of Michigan [Ann Arbor], University of Michigan System, University of South Alabama, Dynamique du noyau [Institut Curie], Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), HAL-SU, Gestionnaire |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
MESH: Signal Transduction
Poly Adenosine Diphosphate Ribose Cell Cycle Proteins Histones Poly ADP Ribosylation 0302 clinical medicine Structural Biology MESH: RNA Small Interfering RNA Small Interfering MESH: Histones 0303 health sciences PARG MESH: X-linked Nuclear Protein biology MESH: Histone Chaperones DNA Neoplasm MESH: Transcription Factors MESH: Gene Expression Regulation Neoplastic Telomere Chromatin Cell biology Gene Expression Regulation Neoplastic MESH: Recombinational DNA Repair Histone MESH: Poly Adenosine Diphosphate Ribose MESH: Epithelial Cells [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Poly(ADP-ribose) Polymerases Signal Transduction G2 Phase X-linked Nuclear Protein MESH: Cell Line Tumor Glycoside Hydrolases DNA repair DNA damage MESH: DNA Neoplasm Article MESH: Chromatin MESH: Telomere Homeostasis Homology directed repair 03 medical and health sciences MESH: Cell Cycle Proteins Cell Line Tumor [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] MESH: Glycoside Hydrolases Humans Histone Chaperones Molecular Biology ATRX 030304 developmental biology MESH: DNA Damage MESH: Humans MESH: Poly ADP Ribosylation MESH: Poly(ADP-ribose) Polymerases Recombinational DNA Repair Telomere Homeostasis Epithelial Cells MESH: G2 Phase MESH: Protein Processing Post-Translational MESH: HeLa Cells biology.protein MESH: Telomere Protein Processing Post-Translational 030217 neurology & neurosurgery DNA Damage HeLa Cells Transcription Factors |
| Zdroj: | Nature Structural and Molecular Biology Nature Structural and Molecular Biology, Nature Publishing Group, 2020, 27 (12), pp.1152-1164. ⟨10.1038/s41594-020-0512-7⟩ Nature Structural & Molecular Biology Nature Structural and Molecular Biology, 2020, 27 (12), pp.1152-1164. ⟨10.1038/s41594-020-0512-7⟩ Nat Struct Mol Biol |
| ISSN: | 1545-9993 1545-9985 |
| DOI: | 10.1038/s41594-020-0512-7⟩ |
| Popis: | International audience; The synthesis of poly(ADP-ribose) (PAR) reconfigures the local chromatin environment and recruits DNA-repair complexes to damaged chromatin. PAR degradation by poly(ADP-ribose) glycohydrolase (PARG) is essential for progression and completion of DNA repair. Here, we show that inhibition of PARG disrupts homology-directed repair (HDR) mechanisms that underpin alternative lengthening of telomeres (ALT). Proteomic analyses uncover a new role for poly(ADP-ribosyl)ation (PARylation) in regulating the chromatin-assembly factor HIRA in ALT cancer cells. We show that HIRA is enriched at telomeres during the G2 phase and is required for histone H3.3 deposition and telomere DNA synthesis. Depletion of HIRA elicits systemic death of ALT cancer cells that is mitigated by re-expression of ATRX, a protein that is frequently inactivated in ALT tumors. We propose that PARylation enables HIRA to fulfill its essential role in the adaptive response to ATRX deficiency that pervades ALT cancers. |
| Databáze: | OpenAIRE |
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