Journal
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
Volume 147, Issue -, Pages 62-76Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbiomolbio.2019.03.001
Keywords
DNA damage; NHEJ; Double-strand breaks; Ku; Protein interactions network; DNA repair machineries; Conserved binding motifs
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Funding
- Ligue Nationale Contre Le Cancer (Equipe labellis 2018)
- Electricite de France (EDF, Conseil de Radioprotection)
- ANR [CE12 2017 NHEJLIG4, ANR-12-SVSE8-012]
- ARC program [SLS220120605310]
- INCA DomRep [PLBIO 2012-280]
- CEFIPRA grant [5203C]
- French Infrastructure for Integrated Structural Biology [ANR-10-INBS-05]
- Ligue Nationale Contre Le Cancer (Equipe labellisee 2018)
- French National Cancer Institut [PLBI017-267]
- Fondation ARC pour la Recherche sur le Cancer [PJA 20171206409]
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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. (C) 2019 Elsevier Ltd. All rights reserved.
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