Molding BRCA2 function through its interacting partners

The role of the tumor suppressor BRCA2 has been shaped over 2 decades thanks to the discovery of its protein and nucleic acid partners, biochemical and structural studies of the protein, and the functional evaluation of germline variants identified in breast cancer patients. Yet, the pathogenic and functional effect of many germline mutations in BRCA2 remains undetermined, and the heterogeneity of BRCA2-associated tumors challenges the identification of causative variants that drive tumorigenesis.In this review, we propose an overview of the established and emerging interacting partners and functional pathways attributed to BRCA2, and we speculate on how variants altering these functions may contribute to cancer susceptibility.