The Spo11 protein and initiation of meiotic recombination. (a) The reaction promoted by the Spo11 protein and subsequent processing of the double-strand break. An active-site Tyr residue acts as nucleophile, attacking the phosphodiester bond. The 3′ hydroxyl is displaced, creating a 5′ phosphotyrosyl-DNA complex. Once the DSB is formed, the broken ends are processed by the action of the Mre11-Rad50-Xrs2 complexes, Sae2 endonuclease, Sgs1 helicase, and ExoI exonuclease or Dna2, which has both helicase and 5′→3′ exonuclease activities. Rad51 or Dmc1 is loaded onto the 3′ extensions (not shown), and strand invasion proceeds. (b) Details of the Spo11 cleavage (transesterification) reaction.