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.

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.

We have investigated the mechanism that enables achiasmate chromosomes to segregate from each other at meiosis I in D. melanogaster oocytes. Using novel cytological methods, we asked whether nonexchange chromosomes are paired prior to disjunction. Our results show that the heterochromatin of homologous chromosomes remains associated throughout prophase until metaphase I regardless of whether they undergo exchange, suggesting that homologous recognition can lead to segregation even in the absence of chiasmata. However, partner chromosomes lacking homology do not pair prior to disjunction. Furthermore, euchromatic synapsis is not maintained throughout prophase. These observations provide a physical demonstration that homologous and heterologous achiasmate segregations occur by different mechanisms and establish a role for heterochromatin in maintaining the alignment of chromosomes during meiosis.

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...

Abstract. Mature Drosophila oocytes are arrested in metaphase of the first meiotic division. We have examined microtubule and chromatin reorganization as the meiosis I spindle assembles on maturation using indirect immunofluorescence and laser scanning confo cal microscopy. The results suggest that chromatin captures or nucleates microtubules, and that these subsequently form a highly tapered spindle in which the majority of microtubules do not terminate at the poles . Nonexchange homologs separate from each other and move toward opposite poles during spindle assembly. By the time of metaphase arrest, these chromosomes are positioned on opposite half spindles, between the metaphase plate and the spindle poles, with the large nonexchange X chromosomes always closer to the metaphase plate than the smaller nonexchange fourth chromosomes . Nonexchange homologs are therefore oriented on the spindle in the absence of a direct ACCURATE chromosome segregation at meiosis I gen-4ACC erally requires recombination between homologs during meiotic prophase, which leads to the physical linkage of homologous chromosomes by chiasmata, which form at sites of meiotic recombination (for review see Hawley, 1988). It is this physical linkage, which forms the bivalents that are aligned on the spindle at metaphase I, that is thought to assure meiotic chromosome disjunction in most systems . A simple mechanical model (Nicklas, 1974), supported by a series ofmicromanipulation studies (Nicklas and Staehly, 1967;Nicklas, 1967;Nicklas and Koch, 1969), explains the need for physically linked homologs during meiosis I. The kinetochores associated with individual homologs are fused into single functional units which capture microtubules from one of the spindle poles. The bivalent then moves toward the pole, as a result of a microtubule-dependent poleward force acting at or near the kinetochore . When the two kinetochores associated with a bivalent are captured by physical linkage, and the spindle position of these chromosomes appears to be determined by size. Lossof-function mutations at the nod locus, which encodes a kinesin-like protein, cause meiotic loss and nondisjunction of nonexchange chromosomes, but have little or no effect on exchange chromosome segregation . In oocytes lacking functional nod protein, most of the nonexchange chromosomes are ejected from the main chromosomal mass shortly after the nuclear envelope breaks down and microtubules interact with the chromatin . In addition, the nonexchange chromosomes that are associated with spindles in nod/nod oocytes show excessive poleward migration . Based on these observations, and the structural similarity of the nod protein and kinesin, we propose that nonexchange chromosomes are maintained on the half spindle by opposing poleward and anti-poleward forces, and that the nod protein provides the anti-poleward force .microtubules from opposite poles, the chiasmata prevent homolog separation and the resulting mechanical tension moves the bivalent to the metaphase plate. Through an unkno...

The synaptonemal complex (SC) is a meiosis-specific scaffold that links homologous chromosomes from end to end during meiotic prophase and is required for the formation of meiotic crossovers. Assembly of SC components is regulated by a combination of associated nonstructural proteins and post-translational modifications, such as SUMOylation, which together coordinate the timing between homologous chromosome pairing, double-strand-break formation and recombination. In addition, transcriptional and translational control mechanisms ensure the timely disassembly of the SC after crossover resolution and before chromosome segregation at anaphase I.

Proper chromosome segregation is crucial for preventing fertility problems, birth defects and cancer. During mitotic cell divisions, sister chromatids separate from each other to opposite poles, resulting in two daughter cells that each have a complete copy of the genome. Meiosis poses a special problem in which homologous chromosomes must first pair and then separate at the first meiotic division before sister chromatids separate at the second meiotic division. So, chromosome interactions between homologues are a unique feature of meiosis and are essential for proper chromosome segregation. Pairing and locking together of homologous chromosomes involves recombination interactions in some cases, but not in others. Although all organisms must match and lock homologous chromosomes to maintain genome integrity throughout meiosis, recent results indicate that the underlying mechanisms vary in different organisms.

Although in Saccharomyces cerevisiae the initiation of meiotic recombination, as indicated by double-strand break formation, appears to be functionally linked to the initiation of synapsis, meiotic chromosome synapsis in Drosophila females occurs in the absence of meiotic exchange. Electron microscopy of oocytes from females homozygous for either of two meiotic mutants (mei-W68 and mei-P22), which eliminate both meiotic crossing over and gene conversion, revealed normal synaptonemal complex formation. Thus, synapsis in Drosophila is independent of meiotic recombination, consistent with a model in which synapsis is required for the initiation of meiotic recombination. Furthermore, the basic processes of early meiosis may have different functional or temporal relations, or both, in yeast and Drosophila.In the classical view of meiosis, homologous chromosome synapsis, as indicated by the formation of an elaborate ribbonlike structure called the synaptonemal complex (SC), was thought to be the first and primary event of meiotic prophase, essential for the initiation of meiotic recombination (1). Studies in Saccharomyces cerevisiae, however, have created a different view of the meiotic process in which the initiation of recombination, as evidenced by a doublestrand break (DSB), precedes the initiation of synapsis (2, 3). Three lines of evidence support this view of early meiotic prophase in yeast. First, the initiating event of meiotic recombination, the formation of a DSB, appears before SC formation (4). Second, meiotic mutants that either fail to create DSBs or to process DSBs to make single-stranded tails prevent the formation of a mature SC (2). Third, some mutants allow high levels of meiotic recombination but prevent the production of a mature SC (5). These data are consistent with a model in which single-stranded DNA generated by a DSB carries out a homology search required for synapsis and SC formation. In contrast, synapsis is not an absolute prerequisite for either the initiation (6) or completion of meiotic recombination (7).To assess the relation between synapsis and the initiation of recombination in Drosophila oocytes, we examined both recombination and SC formation in oocytes homozygous for either of two null-recombination mutations. The mei-W68 and mei-P22 (8) mutants prevent the initiation of meiotic recombination as defined by four independent assays: (i) reduction or elimination of meiotic gene conversion; (ii) elimination of meiotic crossing over, as assayed by measuring either intragenic crossing over or the frequency of meiotic crossing over along entire chromosome arms; (iii) lack of doublestrand DNA breaks that persist into metaphase or anaphase I; and (iv) failure to produce either early or late recombination nodules (RNs).To assay the effects of the mei-W68 and mei-P22 mutations on meiotic crossing over, we examined intragenic recombination at the rosy locus (9). No gene conversion events or intragenic crossovers were observed among the progeny of mei-W68 or mei-P22 females (Table 1 and Fig...