Investigating the role of mimosine-induced genotoxic stress through DNA repair profiling.

Small molecules that induce DNA double-strand breaks (DSBs) are of significant interest for cancer therapy due to their ability to exploit repair vulnerabilities in tumor cells. Mimosine, a non-proteinogenic amino acid derived from Leucaena species, is known to cause cell-cycle arrest and DNA strand breaks, yet its interaction with DNA repair pathways remains poorly understood. Here, we systematically evaluated the genotoxic effects of mimosine in a panel of DNA repair-efficient and deficient cells models. Using neutral comet and γH2Ax assay, we demonstrated that mimosine treatment induces DSBs that persist in cells lacking non-homologous end joining (NHEJ), homologous recombination (HR), and nucleotide excision repair (NER). We established that cells with efficient NHEJ repair pathways can resolve mimosine-induced DNA lesions. Cell cycle analysis shows that mimosine treatment stalls the G1 phase when the NHEJ pathway is active. Cell viability profiling across cancer cells shows greater sensitivity to mimosine in cells with DNA repair deficiency. These findings establish the repair pathway dependencies that drive the mechanism of action of mimosine and its use in cancer treatment therapy.