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Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair

Nature volume 412, pages 607–614 (2001)Cite this article

Abstract

The Ku heterodimer (Ku70 and Ku80 subunits) contributes to genomic integrity through its ability to bind DNA double-strand breaks and facilitate repair by the non-homologous end-joining pathway. The crystal structure of the human Ku heterodimer was determined both alone and bound to a 55-nucleotide DNA element at 2.7 and 2.5 Å resolution, respectively. Ku70 and Ku80 share a common topology and form a dyad-symmetrical molecule with a preformed ring that encircles duplex DNA. The binding site can cradle two full turns of DNA while encircling only the central 3–4 base pairs (bp). Ku makes no contacts with DNA bases and few with the sugar-phosphate backbone, but it fits sterically to major and minor groove contours so as to position the DNA helix in a defined path through the protein ring. These features seem well designed to structurally support broken DNA ends and to bring the DNA helix into phase across the junction during end processing and ligation.

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Figure 1: Overview of the crystal structure.
Figure 2: Structure of the Ku–DNA complex.
Figure 3: Relatedness of human Ku70 and Ku80.
Figure 4: Surface depictions of Ku.
Figure 5: DNA-binding groove.
Figure 6: C-terminal DNA-binding SAP domain of Ku70.

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Acknowledgements

We thank M. Jasin and K. Marians for critical reading of the manuscript; J. Gulbis for assistance with baculovirus production; L. Berman and M. Becker for use of synchrotron facilities at NSLS and C. Heaton at CHESS; and P. Jeffrey for help with synchrotron data collection. This work was supported by grants to J.G. from the NIH, HHMI and Pew Scholars Program in the Biomedical Sciences.

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Author notes

  1. John R. Walker, Richard A. Corpina and Jonathan Goldberg: These authors contributed equally to this work.

Authors and Affiliations

  1. Cellular Biochemistry and Biophysics Program,

    John R. Walker, Richard A. Corpina & Jonathan Goldberg

  2. Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10021, New York, USA

    Jonathan Goldberg

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Correspondence to Jonathan Goldberg.

Additional information

The atomic coordinates have been deposited in the Protein Data Bank under accession numbers 1JEQ and 1JEY.

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Walker, J., Corpina, R. & Goldberg, J. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature 412, 607–614 (2001). https://doi.org/10.1038/35088000

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