The synaptonemal complex (SC) is a protein lattice that resembles railroad tracks and connects paired homologous chromosomes in most meiotic systems. The two side rails of the SC, known as lateral elements (LEs), are connected by proteins known as transverse filaments. The LEs are derived from the axial elements of the chromosomes and play important roles in chromosome condensation, pairing, transverse filament assembly, and prohibiting double-strand breaks (DSBs) from entering into recombination pathways that involve sister chromatids. The proteins that make up the transverse filaments of the SC also play a much earlier role in committing a subset of DSBs into a recombination pathway, which results in the production of reciprocal meiotic crossovers. Sites of crossover commitment can be observed as locations where the SC initiates and as immunostaining foci for a set of proteins required for the processing of DSBs to mature crossovers. In most (but not all) organisms it is the establishment of sites marking such crossover-committed DSBs that facilitates completion of synapsis (full-length extension of the SC). The function of the mature full-length SC may involve both the completion of meiotic recombination at the DNA level and the exchange of the axial elements of the two chromatids involved in the crossover. However, the demonstration that the sites of crossover formation are designated prior to SC formation, and the finding that these sites display interference, argues against a role of the mature SC in mediating the process of interference. Finally, in at least some organisms, modifications of the SC alone are sufficient to ensure meiotic chromosome segregation in the complete absence of meiotic recombination.

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The separation of homologous chromosomes during meiosis in eukaryotes is the physical basis of Mendelian inheritance. The core of the meiotic process is a specialized nuclear division (meiosis I) in which homologs pair with each other, recombine, and then segregate from each other. The processes of chromosome alignment and pairing allow for homolog recognition. Reciprocal meiotic recombination ensures meiotic chromosome segregation by converting sister chromatid cohesion into mechanisms that hold homologous chromosomes together. Finally, the ability of sister kinetochores to orient to a single pole at metaphase I allows the separation of homologs to two different daughter cells. Failures to properly accomplish this elegant chromosome dance result in aneuploidy, a major cause of miscarriage and birth defects in human beings.

The meiotic mutant c(3)G (crossover suppressor on 3 of Gowen) abolishes both synaptonemal complex (SC) formation and meiotic recombination, whereas mutations in the mei-W68 and mei-P22 genes prevent recombination but allow normal SC to form. These data, as well as a century of cytogenetic studies, support the argument that meiotic recombination between homologous chromosomes in Drosophila females requires synapsis and SC formation. We have cloned the c(3)G gene and shown that it encodes a protein that is structurally similar to SC proteins from yeast and mammals. Immunolocalization of the C(3)G protein, as well as the analysis of a C(3)G-eGFP expression construct, reveals that C(3)G is present in a thread-like pattern along the lengths of chromosomes in meiotic prophase, consistent with a role as an SC protein present on meiotic bivalents. The availability of a marker for SC in Drosophila allowed the investigation of the extent of synapsis in exchange-defective mutants. These studies indicate that SC formation is impaired in certain meiotic mutants and that the synaptic defect correlates with the exchange defects. Moreover, the observation of interference among the residual exchanges in these mutant oocytes implies that complete SC formation is not required for crossover interference in Drosophila. Meiotic prophase is marked by interactions between homologous chromosomes that culminate in their alignment with each other along a structure called the synaptonemal complex (SC) (von Wettstein et al. 1984;Zickler and Kleckner 1999;Walker and Hawley 2000). Synapsis and SC formation between homologs is associated with, or requisite for, the formation of exchanges between homologous sequences. These exchanges are later detectable physically as chiasmata, and genetically as recombination between loci on the chromosomes. In many meiotic systems, these genetic exchanges ensure the proper segregation of homologous chromosomes during anaphase I (Hawley 1988).The SC is an almost universally conserved meiotic structure among eukaryotes (von Wettstein et al. 1984;Zickler and Kleckner 1999). After preliminary interactions align homologous chromosomes within ∼300 nm of each other, the chromosomal axes become juxtaposed at a distance of ∼100 nm, which is bridged by the SC. Electron microscopic (EM) studies show the SC as a lattice of transverse filaments (TFs) running between the homologs. The TFs connect the central element, located in the middle of the SC, with lateral elements along the axes of the chromosomes. The connections mediated by the SC are thought to provide a means for holding homologous chromosomes together during meiotic prophase (von Wettstein et al. 1984;Walker and Hawley 2000). In addition, the SC has been proposed to function in the regulation of meiotic recombination and the formation of chiasmata (von Wettstein et al. 1984).Investigations in Saccharomyces cerevisiae, Drosophila melanogaster, and Caenorhabditis elegans have revealed a complex relationship between the SC and the initiation of recombination, whi...

The synaptonemal complex (SC) is intimately involved in the process of meiotic recombination in most organisms, but its exact role remains enigmatic. One reason for this uncertainty is that the overall structure of the SC is evolutionarily conserved, but many SC proteins are not. Two putative SC proteins have been identified in Drosophila: C(3)G and C(2)M. Mutations in either gene cause defects in SC structure and meiotic recombination. Although neither gene is well conserved at the amino acid level, the predicted secondary structure of C(3)G is similar to that of transversefilament proteins, and C(2)M is a distantly related member of the ␣-kleisin family that includes Rec8, a meiosis-specific cohesin protein. Here, we use immunogold labeling of SCs in Drosophila ovaries to localize C(3)G and C(2)M at the EM level. We show that both C(3)G and C(2)M are components of the SC, that the orientation of C(3)G within the SC is similar to other transverse-filament proteins, and that the N terminus of C(2)M is located in the central region adjacent to the lateral elements (LEs). Based on our data and the known phenotypes of C(2)M and C(3)G mutants, we propose a model of SC structure in which C(2)M links C(3)G to the LEs. meiosis ͉ recombination ͉ chromosome ͉ immunogold ͉ electron microscopy I n general terms, the structure of the synaptonemal complex (SC) is conserved among diverse organisms with two lateral elements (LEs) that run along the length of each pair of homologous chromosomes, a central element (CE) that is located midway between the two LEs, and transverse filaments (TF) that connect the LEs to the CE (reviewed in ref. 1). However, distinct differences exist among organisms, particularly in the degree of organization of the CE (2). The conditions required for SC assembly also differ, with DNA double-strand breaks being required for SC formation in some species (e.g., budding yeast, mammals, and plants) but not in others (Drosophila and Caenorhabditis elegans) (3-5). These differences may be useful in defining nonconserved features of SC as well as in highlighting conserved functions.The morphological structures of CEs from a mammal (rat) and two insects (Drosophila and a beetle, Blaps cribrosa) were analyzed at high resolution by using EM tomography (2). In these organisms, the CE structure is essentially the same, but the degree of organization varies considerably. The CE in insects is highly organized, with two (and sometimes more) distinct longitudinal components. These dense longitudinal components appear to be composed of vertical ''pillars'' that link multiple layers of CE together. In comparison, the CE of mammals is less well organized; multiple layers of CE are not obvious, and the longitudinal components are so discontinuous that they typically appear as a single, rather broad, dark structure midway between LEs (2, 6). Some investigators have suggested that the longitudinal components are formed, at least partially, by the Nterminal domains of TFs (7, 8). Whether this difference among species in th...