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The S. cerevisiae Hop2 protein and its fission yeast homolog Meu13 are required for proper homologous chromosome pairing and recombination during meiosis. The mechanism of this requirement is, however, not understood. The previous studies in Saccharomyces suggested that Hop2 is a guardian of meiotic chromosome synapsis with the ability to prevent or resolve deleterious associations between nonhomologous chromosomes. We have generated a Hop2 knockout mouse that shows profound meiotic defects with a distinct and novel phenotype. Hop2−/− spermatocytes arrest at the stage of pachytene-like chromosome condensation. Axial elements are fully developed, but synapsis of any kind is very limited. Immunofluorescence analysis of meiotic chromosome spreads indicates that while meiotic double-stranded breaks are formed and processed in the Hop2 knockout, they fail to be repaired. In aggregate, the Hop2 phenotype is consistent with a direct role for the mouse Hop2 protein in promoting homologous chromosome synapsis. [Copyright &y& Elsevier]