Structural model of full-length human Ku70-Ku80 heterodimer and its recognition of DNA and DNA-PKcs

Angel Rivera-Calzada, Laura Spagnolo, Laurence H Pearl, Oscar Llorca

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Recognition of DNA double-strand breaks during non-homologous end joining is carried out by the Ku70-Ku80 protein, a 150 kDa heterodimer that recruits the DNA repair kinase DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to the lesion. The atomic structure of a truncated Ku70-Ku80 was determined; however, the subunit-specific carboxy-terminal domain of Ku80--essential for binding to DNA-PKcs--was determined only in isolation, and the C-terminal domain of Ku70 was not resolved in its DNA-bound conformation. Both regions are conserved and mediate protein-protein interactions specific to mammals. Here, we reconstruct the three-dimensional structure of the human full-length Ku70-Ku80 dimer at 25 A resolution, alone and in complex with DNA, by using single-particle electron microscopy. We map the C-terminal regions of both subunits, and their conformational changes after DNA and DNA-PKcs binding to define a molecular model of the functions of these domains during DNA repair in the context of full-length Ku70-Ku80 protein.
Original languageEnglish
Pages (from-to)56-62
Number of pages7
JournalEMBO Reports
Issue number1
Publication statusPublished - 2007

Keywords / Materials (for Non-textual outputs)

  • cryo-EM
  • DNA-PK
  • Ku70


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