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Replication protein A 70 kDa DNA-binding subunit (RPA1) is the largest subunit of the heterotrimeric replication protein A complex, a major single-stranded DNA-binding protein in eukaryotes[1][2][3]. RPA1 is essential for DNA metabolism, including DNA replication, repair (especially nucleotide excision and homologous recombination), recombination, and telomere maintenance. It binds to ssDNA regions to protect them from nucleases and secondary structure formation, mediates recruitment of repair and checkpoint factors (such as ATR/ATRIP, RAD51, RAD52, XPA, XPG), and coordinates the response to DNA damage[1][2]. Structurally, RPA1 contains multiple DNA-binding domains and serves as a hub for protein-protein interactions critical to genome integrity. Loss or mutation of RPA1 impairs DNA repair and replication, resulting in increased sensitivity to DNA-damaging agents, and clinical syndromes associated with defective genomic maintenance, such as cancer and bone marrow failure syndromes[1][2][3].
DNA-damaging agents may act by inducing DNA lesions, where RPA1 function is essential for repair[3]. Hypothetical mechanisms for drug targeting might include inhibition of ssDNA binding, disruption of protein-protein interactions in DNA repair complexes, or modulation of DNA damage response pathways, but such drugs are not named in above sources.
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