SUMO-mediated regulation of synaptonemal complex formation during meiosis

The propagation of most sexually reproducing species is possible due to a specialized form of cell division known as meiosis, which leads to the formation of haploid gametes that fuse upon fertilization, reconstituting the species ploidy. A hallmark of meiosis is the ability to segregate homologous chromosomes away from each other, thereby reducing the chromosome set by half. Mechanistically, this involves pairing, synapsis, and the reciprocal exchange of genetic material (crossover recombination) between homologous chromosomes during prophase I. These events ensure that homologs remain physically connected even after they desynapse, allowing for their proper alignment at the metaphase plate and subsequent segregation to opposite poles of the spindle during the first meiotic division. Failures in homolog recognition or in maintaining homologous interactions invariably disrupt meiotic segregation and result in aneuploid gametes. The importance of proper homologous segregation is underscored by the infertility, miscarriages, and various birth defects that trace back to errors in single meiotic events in the paternal or maternal germline progenitors (Hassold and Hunt 2001). Among the various processes that chromosomes undergo during prophase I of meiosis, the establishment of the synaptomenal complex (SC), a proteinaceous framework assembled between homologous chromosomes, is required for the subsequent maintenance of synapsis. While the initial pairing between homologs occurs in the absence of the SC, polymerization of this structure ensures the continuous and stable association (synapsis) along homologous chromosomes throughout pachytene, during which time the completion of reciprocal strand exchange events take place (Page and Hawley 2004). The link between homologous association and recombination is particularly evident in Saccharomyces cerevisiae, where synapsis ultimately depends on double-strand break (DSB) formation. Indeed, in yeast chromosomes, the polymerization of the SC initiates at sites undergoing meiotic recombination (Chua and Roeder 1998) and requires the activities of a DSB-inducing enzyme, as well as of strand invasion/exchange proteins (Giroux et al. 1989; Rockmill et al. 1995; Keeney et al. 1997; Peoples et al. 2002). After DSBs are resolved into either reciprocal crossover or noncrossover repair events, the SC gradually disassembles. The homologs, however, remain associated through chiasmata resulting from the earlier crossover recombination events, underpinned by flanking sister chromatid cohesion. The functional dependency between the formation/disassembly of the SC and maturation of recombination intermediates is intuitive if one considers the importance of preventing DNA exchange between nonhomologous chromosomes and assuring the successful segregation of homologous chromosomes away from each other upon the first meiotic division. However, despite a long history of research focused on the SC since its initial description (Fawcett 1956; Moses 1956), the mechanisms of SC assembly and disassembly within the context of other meiotic events still remain incompletely characterized. In this issue of Genes & Development, new findings by Wang and colleagues (Cheng et al. 2006) reveal a link, in S. cerevisiae, between surnoylation and the regulation of both SC assembly and the propensity of SC proteins to form aggregates known as polycomplexes. They demonstrate that Zip3, a protein involved in the initiation of SC formation, is a SUMO (small ubiquitin-like. modifier) E3 ligase. Moreover, their results suggest that Zip1, a building block of the yeast SC, binds to SUMO-conjugated proteins. These interactions may be important for homology sorting during early prophase, as well as in triggering extensive SC polymerization once homologs are paired during mid-prophase. Apart from introducing surnoylation as a mechanism driving SC polymerization, these findings suggest that SUMO could be similarly involved in the assembly of other complex protein structures.