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The RAD51 recombinase promoter is the regulatory DNA region responsible for controlling the expression of the RAD51 protein, a key enzyme in the homologous recombination (HR) pathway for repairing DNA double-strand breaks [PubMed: 25611383]. This promoter contains various regulatory elements, including binding sites for transcription factors like E2F and p53, which ensure that RAD51 is expressed primarily during the S and G2 phases of the cell cycle when sister chromatids are available for repair [PubMed: 12101419]. In many cancers, the RAD51 promoter is overactive, leading to high levels of RAD51 that help cancer cells survive DNA damage from chemotherapy and radiation [PubMed: 22434704]. Because of this role in treatment resistance, the promoter itself is a target for therapeutic intervention. Strategies include using triplex-forming oligonucleotides (TFOs) to physically block transcription or small molecules to stabilize G-quadruplex structures within the promoter, thereby reducing RAD51 levels and sensitizing tumor cells to DNA-damaging agents [PubMed: 15659510]. However, targeting this region requires high specificity to avoid disrupting DNA repair in healthy cells, which could lead to secondary malignancies or systemic toxicity.
Transcriptional inhibition via triplex DNA formation or stabilization of G-quadruplex structures within the promoter region.
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