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Ad-Rad50 is a recombinant adenoviral vector designed to express a mutant form of the Rad50 protein, specifically the zinc hook domain, while lacking the ATPase and Mre11 interaction domains. It acts as a dominant-negative inhibitor of the Mre11-Rad50-Nbs1 (MRN) complex, which is essential for the repair of DNA double-strand breaks (DSBs). By disrupting the MRN complex, Ad-Rad50 sensitizes cancer cells, particularly nasopharyngeal carcinoma (NPC) cells, to radiotherapy. In preclinical studies, it has been shown to decrease native MRN protein levels, abrogate G2/M arrest, and reduce DNA repair capacity, leading to increased apoptosis and tumor regression when combined with irradiation.
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