Cryo-EM of NHEJ supercomplexes provides insights into DNA repair

0301 basic medicine 0303 health sciences DNA End-Joining Repair DNA Repair Cryoelectron Microscopy DNA repair long-range synaptic complexes Apoptosis DNA-Activated Protein Kinase Article non-homologous end joining DNA-PK DNA-Binding Proteins DNA Ligase ATP 03 medical and health sciences DNA Repair Enzymes Multiprotein Complexes cryo-EM Humans DNA Breaks, Double-Stranded Phosphorylation Ku Autoantigen NHEJ DNA Damage
DOI: 10.1016/j.molcel.2021.07.005 Publication Date: 2021-08-04T14:31:14Z
ABSTRACT
Non-homologous end joining (NHEJ) is one of two critical mechanisms utilized in humans to repair DNA double-strand breaks (DSBs). Unrepaired or incorrect DSBs can lead apoptosis cancer. NHEJ involves several proteins, including the Ku70/80 heterodimer, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), X-ray cross-complementing 4 (XRCC4), XRCC4-like factor (XLF), and ligase IV. These core proteins bind ligate damaged ends. However, details structural assembly these remain unclear. Here, we present cryo-EM structures supercomplexes that are composed DNA, revealing detailed architecture this assembly. We describe monomeric dimeric forms supercomplex also propose existence alternate long-range synaptic complexes. Finally, show mutational disruption features within complexes negatively affects repair.
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