Here, using an I-SceI-cleavable reporter assay based on the human endogenous HPRT gene (50,51), together with an array of I-SceI-cleavable GFP-based reporter assays (52–54), in different cancer cell lines we have established a role for HR factors in suppressing mutagenic MMEJ following DSB resection. This evidence concerns the gene HPRT1 and cancer.