MAD2L2 and neoplasm: Two genetic mechanisms of emerging PARP inhibitor resistance in HR-deficient cells and tumours have been documented in the literature: suppressor mutations in genes such as 53BP135 and REV7,36 or secondary mutations that restore the function of the originally mutated HR genes such as BRCA1,37BRCA2,38,39RAD51C or RAD51D. 40 We did not observe the evolution of resistance by either mechanism, though the large deletion in BRCA1 in DT40 cells precluded genetic reversion.