259: Ku filaments that hold DNA together
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259: Ku filaments that hold DNA together
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Zahid S et al., Nat Commun - Cryo-EM and biophysical analyses show Mycobacterium tuberculosis Ku assembles into DNA-bound oligomeric filaments that synapse DNA ends and are required for survival under DNA-damaging conditions.
Study Highlights:
Deletion of ku in M. smegmatis causes marked survival defects after methyl methanesulfonate exposure and desiccation that are rescued by complementation. Cryo-EM structures of apo-Ku-Mtb (4.04 Å) and DNA-bound Ku-Mtb (2.96 Å) reveal a homodimer that assembles into extended filaments with a minimal repeating unit of two homodimers per DNA duplex. Biophysical assays (mass photometry, FIDA, AFM) and positive-stain EM confirm DNA-induced oligomerisation and show Ku can circularize DNA ends, holding them ~40 Å apart. Mutation of hydrophobic loop residues L13/V14 abolishes filament formation while preserving DNA binding and reduces bacterial survival, and the C-terminal α-helix blocks the filament interface in the apo state and is displaced on DNA binding to enable LigD recruitment.
Conclusion:
Ku oligomerisation mediates DNA end synapsis during bacterial NHEJ and is critical for mycobacterial survival under DNA-damaging stresses
Music:
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Reference:
Zahid S, Baconnais S, Smith H, Atwal S, Bates L, Read H, Chadda A, Morati F, Stender EGP, Westerlund F, Galburt E, Mukamolova GV, Chaplin AK, et al. Oligomerisation of Ku from Mycobacterium tuberculosis promotes DNA synapsis. Nature Communications. 2025;16:10568. https://doi.org/10.1038/s41467-025-65609-y
License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/
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