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Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1

Nature Structural & Molecular Biology volume 8, pages 838–842 (2001) Cite this article

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Abstract

The C-terminal BRCT region of BRCA1 is essential for its DNA repair, transcriptional regulation and tumor suppressor functions. Here we determine the crystal structure of the BRCT domain of human BRCA1 at 2.5 Å resolution. The domain contains two BRCT repeats that adopt similar structures and are packed together in a head-to-tail arrangement. Cancer-causing missense mutations occur at the interface between the two repeats and destabilize the structure. The manner by which the two BRCT repeats interact in BRCA1 may represent a general mode of interaction between homologous domains within proteins that interact to regulate the cellular response to DNA damage. The structure provides a basis to predict the structural consequences of uncharacterized BRCA1 mutations.

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Figure 1: The two BRCT repeats form a single protein domain.
Figure 2: The structure of the dual repeat BRCT domain of BRCA1.
Figure 3: The packing of BRCT repeats.
Figure 4: Analysis of the structural consequences of mutations in the BRCT domain.

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References

  1. Miki, Y. et al. Science 266, 66–71 (1994).

    Article  CAS  Google Scholar 

  2. Futreal, P.A. et al. Science 266, 120–122 (1994).

    Article  CAS  Google Scholar 

  3. Friedman, L.S. et al. Nature Genet. 8, 399–404 (1994).

    Article  CAS  Google Scholar 

  4. Gayther, S.A. et al. Am. J. Hum. Genet. 58, 451–456 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Koonin, E.V., Altschul, S.F. & Bork, P. Nature Genet. 13, 266–268 (1996).

    Article  CAS  Google Scholar 

  6. Callebaut, I. & Mornon, J.P. FEBS Lett. 400, 25–30 (1997).

    Article  CAS  Google Scholar 

  7. Cantor, S.B. et al. Cell 105, 149–160 (2001).

    Article  CAS  Google Scholar 

  8. Deng, C.X. & Brodie, S.G. Bioessays 22, 728–737 (2000).

    Article  CAS  Google Scholar 

  9. Terwilliger, T.C. & Berendzen, J. Acta Crystallogr. D 55, 849–861 (1999).

    Article  CAS  Google Scholar 

  10. Zhang, X. et al. EMBO J. 17, 6404–6411 (1998).

    Article  CAS  Google Scholar 

  11. Lee, J.Y. et al. EMBO J. 19, 1119–1129 (2000).

    Article  CAS  Google Scholar 

  12. Nash, R.A., Caldecott, K.W., Barnes, D.E. & Lindahl, T. Biochemistry 36, 5207–5211 (1997).

    Article  CAS  Google Scholar 

  13. Dulic, A. et al. Biochemistry 40, 5906–5211 (2001).

    Article  CAS  Google Scholar 

  14. Scully, R. et al. Mol. Cell 4, 1093–1099 (1999).

    Article  CAS  Google Scholar 

  15. Yu, X., Wu, L.C., Bowcock, A.M., Aronheim, A. & Baer, R. J. Biol. Chem. 273, 25388–25392 (1998).

    Article  CAS  Google Scholar 

  16. Li, S. et al. J. Biol. Chem. 274, 11334–11338 (1999).

    Article  CAS  Google Scholar 

  17. Yarden, R.I. & Brody, L.C. Proc. Natl. Acad. Sci. USA 96, 4983–4988 (1999).

    Article  CAS  Google Scholar 

  18. Chapman, M.S. & Verma, I.M. Nature 382, 678–679 (1996).

    Article  CAS  Google Scholar 

  19. http://www.nhgri.nih.gov/Intramural_research/Lab_transfer/Bic/

  20. Eriksson, A.E. et al. Science 255, 178–183 (1992).

    Article  CAS  Google Scholar 

  21. Otwinowski, Z. & Minor, W. Methods Enzymol. 276, 307–325 (1997).

    Article  CAS  Google Scholar 

  22. Cowtan, K. In Joint CCP4 and ESF-EACBM newsletter on protein crystallography 31, 34–38 (1994).

  23. Jones, T.A., Zou, J.Y., Cowan, S.W. & Kjeldgaard Acta Crystallogr. A 47, 110–119 (1991).

    Article  Google Scholar 

  24. Brünger, A.T. et al. Acta Crystallogr. D 54, 905–921 (1998).

    Article  Google Scholar 

  25. Collaborative Computational Project, Number 4. Acta Crystallogr. D 50, 760–763 (1994).

  26. Winn, M.D., Isupov, M.N. & Murshudov, G.N. Acta Crystallogr. D 57, 122–133 (2001).

    Article  CAS  Google Scholar 

  27. Laskowski, R.A., MacArthur, M.W. & Thornton, J.M. Curr. Opin. Struct. Biol. 8, 631–639 (1998).

    Article  CAS  Google Scholar 

  28. Kraulis, P.J. J. Appl. Crystallogr. 24, 946–950 (1991).

    Article  Google Scholar 

  29. Merritt, E.A. & Bacon, D.J. Methods Enzymol. 277, 505–524 (1997).

    Article  CAS  Google Scholar 

  30. POV-Team. Persistence of Vision Ray Tracer v.3.1 http://www.povray.org (1999).

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Acknowledgements

We would like to thank L. Gaudreau for the gift of the BRCA1(1,568–1,863) expression plasmid and helpful discussions, B. Mark and J. Lamoureux for help with X-ray data collection, and K. Brister and the staff of APS BioCARS for excellent technical support during synchrotron data collection. This work was supported by operating grants from the Canadian Institutes of Health Research, the Canadian Breast Cancer Research Initiative and the Alberta Heritage Foundation for Medical Research.

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  1. Department of Biochemistry, University of Alberta, Edmonton, T6G 2H7, Alberta, Canada

    R. Scott Williams, Ruth Green & J.N. Mark Glover

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  1. R. Scott Williams
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  2. Ruth Green
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  3. J.N. Mark Glover
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Correspondence to J.N. Mark Glover.

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Williams, R., Green, R. & Glover, J. Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1. Nat Struct Mol Biol 8, 838–842 (2001). https://doi.org/10.1038/nsb1001-838

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