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Meiotic recombination protein Spo11 (SPO11) is a highly conserved enzyme that initiates meiotic recombination by generating programmed DNA double-strand breaks (DSBs) during the early stages of meiosis[2][3]. SPO11 is a functional homolog of the archaeal type II topoisomerase VI A subunit and employs a catalytic tyrosine residue to cleave DNA and become covalently linked to the 5' DNA termini at break sites[1][2][3]. This cleavage is essential for homologous recombination and proper chromosome segregation in sexually reproducing organisms. SPO11 functions as part of a larger protein complex with multiple partners; its activity is tightly regulated and is specific to meiotic cells in most species[2][3]. Mutations in SPO11 or its regulatory partners cause defects in fertility due to failures in chromosome synapsis and recombination. While SPO11 is not a current drug target (no drugs are known to interact directly with it), its classification as a cancer/testis antigen makes it a biomarker candidate for certain malignancies and a potential immunotherapy target in testis-specific cancers[3].
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