Abstract
The DNA repair protein Rad51 is known to be involved in the Homologous recombination-mediated DNA double-strand breaks (DSBs) repair. Prodigiosin (PG), a secondary metabolite, belongs to a family of tripyrrole red pigments produced by a group of Streptomyces and Serratia strains. PG has previously been shown to induce DSBs by penetrating the plasma membrane and incorporating into DNA. However, the correlation between PG and Rad51 remains unclear. In present study, we demonstrate the PG-regulated mechanism controls RAD51 function. Treatment of PG resulted in decreased protein and mRNA of Rad51 by suppressing promoter activity, but not by proteasome-mediated degradation. In the p53 knockdown experiment, we found that p53 is not involved in the pathway of PG deceased RAD51 protein. Inhibition of PG-stimulated p38 and JNK activation by SB203580 and SP600125 showed to rescue PG-inhibited RAD51 expression. Importantly, overexpression RAD51 further showed that the cytotoxic effect of PG was decreased. In conclusion, RAD51 plays an important role in PG’s cytotoxic effect. And we identify RAD51 as a novel molecular target of PG. Moreover, we found that treatment of cisplatin or adriamycin stimulated RAD51 expression. Together these results suggest that combination of cisplatin or adriamycin with PG may enhance the cytotoxic effect and reduce the dosage.
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