BRCA1 and cancer: Despite the ease of gene inactivation by homologous gene targeting, the similarity of HR rates in DT40 and cultured human cell lines has been demonstrated by, for example, similar sister chromatid exchange rates per chromosome,40, 41 and DT40 mutants have been used extensively for studying the genetics of HR.42 The similarity of the mutation patterns to signature 3 associated with BRCA1/2 mutant cancers confirms the validity of the cell line model, and suggests that these cancers also have a higher mutation rate.