Cryo-EM of NHEJ supercomplexes provides insights into DNA repair
| Autor: | Antonia Kefala Stavridi, Virginie Ropars, Shikang Liang, Amanda K. Chaplin, Jean-Baptiste Charbonnier, Dimitri Y. Chirgadze, Steven W. Hardwick, Noah J Goff, Tom L. Blundell, Taiana Maia de Oliveira, Katheryn Meek, Christopher J. Buehl |
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| Přispěvatelé: | Hardwick, Steven [0000-0001-9246-1864], Liang, Shikang [0000-0002-6930-7882], Chirgadze, Dima [0000-0001-9942-0993], Blundell, Tom [0000-0002-2708-8992], Apollo - University of Cambridge Repository |
| Rok vydání: | 2021 |
| Předmět: |
DNA End-Joining Repair
DNA Repair DNA repair DNA damage long-range synaptic complexes Apoptosis DNA-Activated Protein Kinase Biology non-homologous end joining DNA-PK chemistry.chemical_compound DNA Ligase ATP Humans DNA Breaks Double-Stranded Phosphorylation Molecular Biology Ku Autoantigen NHEJ chemistry.chemical_classification DNA ligase Ku70 fungi Cryoelectron Microscopy Cell Biology DNA repair protein XRCC4 Cell biology Non-homologous end joining DNA-Binding Proteins enzymes and coenzymes (carbohydrates) DNA Repair Enzymes chemistry Multiprotein Complexes cryo-EM DNA DNA Damage |
| DOI: | 10.17863/cam.72535 |
| Popis: | Non-homologous end joining (NHEJ) is one of two critical mechanisms utilized in humans to repair DNA double-strand breaks (DSBs). Unrepaired or incorrect repair of DSBs can lead to apoptosis or cancer. NHEJ involves several proteins, including the Ku70/80 heterodimer, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), X-ray cross-complementing protein 4 (XRCC4), XRCC4-like factor (XLF), and ligase IV. These core proteins bind DSBs and ligate the damaged DNA ends. However, details of the structural assembly of these proteins remain unclear. Here, we present cryo-EM structures of NHEJ supercomplexes that are composed of these core proteins and DNA, revealing the detailed structural architecture of this assembly. We describe monomeric and dimeric forms of this supercomplex and also propose the existence of alternate dimeric forms of long-range synaptic complexes. Finally, we show that mutational disruption of several structural features within these NHEJ complexes negatively affects DNA repair. |
| Databáze: | OpenAIRE |
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