Plugged into the Ku-DNA hub: The NHEJ network. (October 2019)

• Record Type: Journal Article
• Authors: Frit, Philippe; Ropars, Virginie; Modesti, Mauro; Charbonnier, Jean Baptiste; Calsou, Patrick
• Is Part Of: Progress in biophysics and molecular biology. Volume 147(2019)
• Page Start: 62
• Page End: 76
• Publication Date: 2019-10
• Subjects: DNA damage -- NHEJ -- Double-strand breaks -- Ku -- Protein interactions network -- DNA repair machineries -- Conserved binding motifs; APLF APTX and PNKP-like factor -- BRCT BRCA1 C-Terminus domain -- Cryo-EM cryo-electron microscopy -- CTD C-terminal domain -- CYREN cell-cycle regulator of NHEJ -- DNA-PK DNA-dependent protein kinase -- DNA-PKcs DNA-PK catalytic subunit -- ds double-stranded -- DSB DNA double strand break -- EMSA electrophoretic mobility shift assay -- HEAT Huntington, Elongation Factor 3 -- PR65/A TOR domain -- FAT, FRAP ATM and TRRAP domain -- FATC FAT and C-terminal domain -- FHA forkhead associated domain -- IR ionizing radiation -- KBM Ku-binding motif -- KD kinase domain -- MRI modulator of retroviral infection -- NAP1L nucleosome assembly protein 1-like domain -- PAXX paralog of XRCC4 and XLF -- PBZ PAR Binding Zinc finger domain -- PI3K phosphatidyl inositol 3 kinase -- PIKK phosphatidyl inositol-3 kinase-like protein kinase -- PNKP Polynucleotide Kinase/Phosphatase -- RAG1 Recombination activating gene 1 -- TDP1 Tyrosyl-DNA phosphodiesterase 1 -- TdT terminal deoxynucleotidyl transferase -- Top1, Top2 DNA topoisomerase 1, 2 -- vWA von Willebrand factor type A -- XLF XRCC4-Like Factor -- WS Werner Syndrome; Biophysics -- Periodicals; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular Biology -- Periodicals; Biophysique -- Périodiques; Biochimie -- Périodiques; 571.4
• DOI: 10.1016/j.pbiomolbio.2019.03.001
• Languages: English
• ISSNs: 0079-6107

Abstract

Abstract: In vertebrates, double-strand breaks in DNA are primarily repaired by Non-Homologous End-Joining (NHEJ). The ring-shaped Ku heterodimer rapidly senses and threads onto broken DNA ends forming a recruiting hub. Through protein-protein contacts eventually reinforced by protein-DNA interactions, the Ku-DNA hub attracts a series of specialized proteins with scaffolding and/or enzymatic properties. To shed light on these dynamic interplays, we review here current knowledge on proteins directly interacting with Ku and on the contact points involved, with a particular accent on the different classes of Ku-binding motifs identified in several Ku partners. An integrated structural model of the core NHEJ network at the synapsis step is proposed.