Computationally-designed aptamers targeting RAD51-BRCA2 interaction impair homologous recombination and induce synthetic lethality.

ABSTRACT: The interaction between RAD51 and BRCA2 plays a key role in homologous recombination (HR), a critical DNA repair mechanism essential for the survival of cancer cells. Disrupting this interaction increases the sensitivity of cancer cells to chemotherapeutic agents. Here, we employed in silico methods to design aptamers-customized single-stranded oligonucleotides-specifically engineered to bind RAD51. These aptamers were developed with the aim of selectively modulating RAD51's nuclear recruitment and its role in DNA repair processes. The leading candidate displays high affinity for RAD51, competing with BRCA2 for the same interaction site in vitro, as confirmed through biolayer interferometry (BLI) and fluorescence lifetime imaging microscopy (FLIM). In pancreatic cancer cells, we show that

SUBMITTER: Milordini G 

PROVIDER: S-EPMC12770486 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature