A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization

The cancer-associated D2723H mutation causes mislocalization of BRCA2 to the cytoplasm. New work shows that this mutation disrupts the interaction of BRCA2 with DSS1, unmasking a BRCA2 nuclear export signal within the DSS1 binding domain. This impairs nuclear retention of BRCA2 and, consequently, RAD51, suggesting that the intracellular localization of these factors may control their function in maintaining genome integrity.