We used the karyotypically stable, near-diploid colorectal cancer cell line HCT116 as a model system (McLellan et al. 2012; McManus et al. 2009).We targeted MCM2, MCM10, GINS1/PSF1, CDC45L, and POLA1 for knockdown by siRNA and asked whether these treatments sensitized cells to chemical inhibition of MRE11A with mirin, a recently described inhibitor of Mre11-Rad50-Nbs1 complex activity (Dupre et al. 2008). The gene discussed is RAD50; the disease is colorectal cancer.