The Mus81 solution to resolution: generating meiotic crossovers without Holliday junctions.

During meiosis, recombination between homologous chromosomes creates a physical connection that is necessary for proper chromosome segregation at the first meiotic division. For many years, the paradigm used to explain the molecular mechanism of recombination has been the double-strand break repair (DSBR) model (Fig. 1; Szostak et al. 1983). (The definitions of the acronyms used in this review, in order of their appearance, can be found in Table 1.) One key feature of this model is that recombination is initiated by the formation of programmed DSBs (double-strand breaks). The meiosis-specific protein responsible for catalyzing these breaks is a topoisomerase-like protein called Spo11 (Bergerat et al. 1997; Keeney et al. 1997). The identification and functional analysis of Spo11 homologs from a wide variety of organisms, including worms, fruit flies, fission yeast, and mammals, indicates that repair of programmed DSBs is a universal feature of meiotic recombination (Keeney 2001). A second key feature of the model is the generation of a recombination intermediate called a double Holliday junction (dHJ). Differential resolution of this intermediate was proposed to determine the formation of crossover (CO) versus noncrossover (NCO) chromosomes. Recent advances indicate, however, that the decision of whether a recombination event will result in a CO or NCO chromosome occurs much earlier, soon after DSB formation (Allers and Lichten 2001a; Hunter and Kleckner 2001; Clyne et al. 2003). In addition, studies of a newly discovered endonuclease, Mus81, indicate that, in addition to dHJ resolution, COs may be formed by the processing of non-dHJ intermediates (Heyer et al. 2003; Osman et al. 2003). The decision of which crossover pathway to use appears to vary between organisms and may, therefore, be evolutionarily significant (de los Santos et al. 2003). The double-strand break repair model for meiotic recombination