BRCA2 and cancer: To test this prediction, we compared ISG15 protein levels in isogenic pairs of BRCA1/2-deficient and -proficient cancer cells and found a consistent upregulation of ISG15 in cells carrying defects in either BRCA1 or BRCA2 (Fig. 6a), suggesting that it may be required for the fitness of BRCA1/2-deficient cells.