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

Rivera-Calzada, A., Spagnolo, L. , Pearl, L. H. and Llorca, O. (2006) Structural model of full-length human Ku70-Ku80 heterodimer and its recognition of DNA and DNA-PKcs. EMBO Reports, 8, pp. 56-62. (doi: 10.1038/sj.embor.7400847) (PMID:17159921) (PMCID:PMC1796749)

Abstract

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 Å 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Spagnolo, Professor Laura
• Authors: Rivera-Calzada, A., Spagnolo, L., Pearl, L. H., and Llorca, O.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: EMBO Reports
• Publisher: EMBO Press
• ISSN: 1469-221X
• ISSN (Online): 1469-3178