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RAD52 mRNA encodes the DNA repair protein RAD52 homolog, a critical mediator of DNA double-strand break repair via the homologous recombination (HR) and single-strand annealing (SSA) pathways (Source: UniProt P43351). While RAD52 is largely redundant in normal human cells, it becomes essential for the survival of cells lacking functional BRCA1 or BRCA2 proteins, a phenomenon known as synthetic lethality (Source: PubMed 21743466). This dependency makes RAD52 mRNA an attractive therapeutic target for treating cancers with homologous recombination deficiencies, such as certain breast, ovarian, and prostate cancers (Source: PubMed 23513434). Therapeutic strategies targeting the mRNA, including small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs), aim to deplete RAD52 protein levels to selectively kill tumor cells while sparing healthy ones (Source: PubMed 25611625). Experimental studies have demonstrated that knocking down RAD52 mRNA significantly reduces the viability of BRCA-mutant cells without affecting wild-type cells (Source: PubMed 23513434). However, the clinical application of RAD52 mRNA-targeted therapies faces hurdles such as the need for effective systemic delivery systems and the potential for off-target RNA interactions (Source: PubMed 25611625).
RNA interference (RNAi) and antisense-mediated degradation of RAD52 mRNA, which prevents the translation of the RAD52 protein and disrupts the single-strand annealing and alternative homologous recombination pathways in BRCA-deficient cells.
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