Article

Nature 420, 287-293 (21 November 2002) | doi:10.1038/nature01230; Received 1 July 2002; Accepted 21 October 2002; Published online 10 November 2002

Insights into DNA recombination from the structure of a RAD51–BRCA2 complex

Luca Pellegrini1, David S. Yu2,3, Thomas Lo1,3, Shubha Anand2, MiYoung Lee2, Tom L. Blundell1 & Ashok R. Venkitaraman2

  1. University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge CB2 1GA, UK
  2. University of Cambridge, CR UK Department of Oncology and The Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK
  3. These authors contributed equally to this work

Correspondence to: Ashok R. Venkitaraman2 Correspondence and requests for materials should be addressed to A.R.V. (e-mail: Email: arv22@cam.ac.uk). The coordinates have been deposited in the Protein Data Bank under accession code 1n0w.

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The breast cancer susceptibility protein BRCA2 controls the function of RAD51, a recombinase enzyme, in pathways for DNA repair by homologous recombination. We report here the structure of a complex between an evolutionarily conserved sequence in BRCA2 (the BRC repeat) and the RecA-homology domain of RAD51. The BRC repeat mimics a motif in RAD51 that serves as an interface for oligomerization between individual RAD51 monomers, thus enabling BRCA2 to control the assembly of the RAD51 nucleoprotein filament, which is essential for strand-pairing reactions during DNA recombination. The RAD51 oligomerization motif is highly conserved among RecA-like recombinases, highlighting a common evolutionary origin for the mechanism of nucleoprotein filament formation, mirrored in the BRC repeat. Cancer-associated mutations that affect the BRC repeat disrupt its predicted interaction with RAD51, yielding structural insight into mechanisms for cancer susceptibility.