MEIOSIS-SPECIFIC DNA DOUBLE-STRAND BREAKS ARE CATALYZED BY SPO11, A MEMBER OF A WIDELY CONSERVED PROTEIN FAMILY

Meiotic recombination in S. cerevisiae is initiated by double-strand b reaks (DSBs). In certain mutants, breaks accumulate with a covalently attached protein, suggesting that cleavage is catalyzed by the DSB-ass ociated protein via a topoisomerase-like transesterase mechanism. We h ave purified these protein-DNA complexes and identified the protein as Spo11, one of several proteins required for DSB formation. These find ings strongly implicate Spo11 as the catalytic subunit of the meiotic DNA cleavage activity. This is the first identification of a biochemic al function for any of the gene products involved in DSB formation. Sp o11 defines a protein family with other members in fission yeast, nema todes, and archaebacteria. The S. pombe homolog, rec12p, is also known to be required for meiotic recombination. Thus, these findings provid e direct evidence that the mechanism of meiotic recombination initiati on is evolutionarily conserved.