The tumor suppressor breast cancer susceptibility protein 1 (BRCA1) protects our 
cells from genomic instability in part by facilitating the efficient repair of 
DNA double-strand breaks (DSBs). BRCA1 promotes the error-free repair of DSBs 
through homologous recombination and is also implicated in the regulation of 
nonhomologous end joining (NHEJ) repair fidelity. Here, we investigate the role 
of BRCA1 in NHEJ repair mutagenesis following a DSB. We examined the frequency 
of microhomology-mediated end joining (MMEJ) and the fidelity of DSB repair 
relative to BRCA1 protein levels in both control and tumorigenic breast 
epithelial cells. In addition to altered BRCA1 protein levels, we tested the 
effects of cellular exposure to mirin, an inhibitor of meiotic recombination 
enzyme 11 (Mre11) 3'-5'-exonuclease activity. Knockdown or loss of BRCA1 protein 
resulted in an increased frequency of overall plasmid DNA mutagenesis and MMEJ 
following a DSB. Inhibition of Mre11-exonuclease activity with mirin 
significantly decreased the occurrence of MMEJ, but did not considerably affect 
the overall mutagenic frequency of plasmid DSB repair. The results suggest that 
BRCA1 protects DNA from mutagenesis during nonhomologous DSB repair in 
plasmid-based assays. The increased frequency of DSB mutagenesis and MMEJ repair 
in the absence of BRCA1 suggests a potential mechanism for carcinogenesis.