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Exonuclease 1 (EXO1) is an evolutionarily conserved exonuclease enzyme of the Rad2/XPG family, implicated in multiple DNA metabolic processes, including DNA mismatch repair, double-strand break resection, DNA replication, telomere maintenance, and meiotic recombination. As an enzyme, EXO1 possesses both 5′ to 3′ exonuclease and 5′-flap endonuclease activities, facilitating the precise processing of DNA intermediates during repair and replication. EXO1’s enzymatic activity is essential for maintaining genomic stability, suppressing tumors, and is also important for antibody diversification through somatic hypermutation and class switch recombination in B cells. Structurally, EXO1 also acts as a scaffold in some DNA repair complexes, independent of its catalytic activity. Impaired EXO1 function or mutations are associated with increased cancer susceptibility, especially colorectal cancer, abnormal immune responses, and infertility due to meiotic failure. Although not currently a direct therapeutic target with approved drugs, its central role in DNA repair processes makes it a strong candidate for research in oncology and genome instability syndromes.
Not applicable to approved drugs as of 2024. Theoretically, an EXO1 inhibitor would reduce exonuclease activity, leading to increased DNA repair defects, genomic instability, or sensitivity to DNA-damaging agents.
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