Journal
EMBO REPORTS
Volume 10, Issue 9, Pages 990-996Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/embor.2009.126
Keywords
PALB2; BRCA2; DNA repair; homologous recombination; cancer
Categories
Funding
- Cancer Research UK [C302/A8265, C302/A7803]
- National Health Service
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The breast cancer 2, early onset protein (BRCA2) is central to the repair of DNA damage by homologous recombination. BRCA2 recruits the recombinase RAD51 to sites of damage, regulates its assembly into nucleoprotein filaments and thereby promotes homologous recombination. Localization of BRCA2 to nuclear foci requires its association with the partner and localizer of BRCA2 (PALB2), mutations in which are associated with cancer predisposition, as well as subtype N of Fanconi anaemia. We have determined the structure of the PALB2 carboxy terminal beta-propeller domain in complex with a BRCA2 peptide. The structure shows the molecular determinants of this important protein protein interaction and explains the effects of both cancer associated truncating mutants in PALB2 and missense mutations in the amino terminal region of BRCA2.
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