In the absence of wild type nibrin in fibroblasts, irradiation leads to an increased proportion of base transversions (Fig. 2B), sug- gesting that this particular mutation can be attributed to the DSB repair deficiency caused by nibrin loss. In contrast, as shown in Fig. 4A, the increased basal mutation frequency in the humanised NBS mice in vivo is characterised by base transitions rather than transversions. Again, fewer complex mutations, the consequence of recombination events, are observed in the humanised mice than in control mice.