Explore the vast range of titles available.

The synaptonemal complex (SC) connects homologous chromosomes in meiotic prophase, thus promoting genetic exchange and ensuring accurate chromosomal segregation at anaphase. In this Review, the authors discuss the structural organization of the SC and how its assembly, maintenance and disassembly are regulated in yeast and metazoans. The synaptonemal complex (SC) connects homologous chromosomes in meiotic prophase, thus promoting genetic exchange and ensuring accurate chromosomal segregation at anaphase. In this Review, the authors discuss the structural organization of the SC and how its assembly, maintenance and disassembly are regulated in yeast and metazoans. 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.

Meiotic recombination generates crossovers (COs), reciprocal exchanges between homologous chromosomes critical for accurate chromosome segregation. Inappropriate CO frequency and distribution drive aneuploidy in human oocytes, with error rates up to 10-fold higher than in sperm despite females exhibiting higher CO frequencies. COs form in the context of the proteinaceous synaptonemal complex (SC) that tethers homologs during prophase I. SC length strongly correlates with CO number, and sexual dimorphism in recombination has long been attributed to longer SCs in females. However, this model is challenged by wild-derived PWD mice in which males consistently generate more COs despite having shorter SCs. Here, we exploit natural genetic variation among inbred mouse strains to dissect the structural and regulatory basis of sexually dimorphic CO regulation. Using cytological markers of SC assembly (SYCP3), recombination progression (RAD51, MSH4), class I CO designation (HEI10, MLH1/MLH3), and chiasmata, we show that SC length is not the sole predictor of CO number. PWD males exhibit stronger CO interference and higher CO number than females, despite reduced SC length. Notably, females show reduced efficiency in designating recombination intermediates to become COs, whereas PWD males display exceptional proficiency. Unexpectedly, although class II COs are rare, they play a disproportionate role in ensuring that every chromosome pair receives at least one CO, thereby safeguarding against aneuploidy. Together, these findings challenge the prevailing view that SC length is the primary determinant of sexually dimorphic CO rates and instead highlight sex-specific regulation of CO designation and pathway usage as key drivers of recombination outcomes.

DNA double-strand breaks (DSBs) are induced by SPO11 during meiosis to initiate recombination-mediated pairing and synapsis of homologous chromosomes. Germline genome integrity requires spatiotemporal control of DSB formation, which involves the proteinaceous chromosome axis along the core of each meiotic chromosome. In particular, a component of unsynapsed axes, HORMAD1, promotes DSB formation in unsynapsed regions where DSB formation must occur to ensure completion of synapsis. Despite its importance, the underlying mechanism has remained elusive. We identify CCDC36 as a direct interactor of HORMAD1 (IHO1) that is essential for DSB formation. Underpinning this function, IHO1 and conserved SPO11-auxiliary proteins MEI4 and REC114 assemble chromatin-bound recombinosomes that are predicted activators of DSB formation. HORMAD1 is needed for robust recruitment of IHO1 to unsynapsed axes and efficient formation and/or stabilization of these recombinosomes. Thus, we propose that HORMAD1–IHO1 interaction provides a mechanism for the selective promotion of DSB formation along unsynapsed chromosome axes. In meiosis, double-strand breaks (DSBs) are induced to initiate chromosome pairing and synapsis. Stanzione et al.  identify IHO1 as a protein recruited by HORMAD1 to unsynapsed chromosome axes and required for DSB formation.

The synaptonemal complex (SC) is a polymer that spans ~100 nm between paired homologous chromosomes during meiosis. Its striated, periodic appearance in electron micrographs led to the idea that transverse filaments within this structure ‘crosslink’ the axes of homologous chromosomes, stabilizing their pairing. SC proteins can also form polycomplexes, three-dimensional lattices that recapitulate the periodic structure of SCs but do not associate with chromosomes. Here we provide evidence that SCs and polycomplexes contain mobile subunits and that their assembly is promoted by weak hydrophobic interactions, indicative of a liquid crystalline phase. We further show that in the absence of recombination intermediates, polycomplexes recapitulate the dynamic localization of pro-crossover factors during meiotic progression, revealing how the SC might act as a conduit to regulate chromosome-wide crossover distribution. Properties unique to liquid crystals likely enable long-range signal transduction along meiotic chromosomes and underlie the rapid evolution of SC proteins. The genetic information in cells is encoded within long molecules of DNA called chromosomes. In most human cells, the two copies of each chromosome – the one inherited from our mother and the one from our father – are physically separated and behave independently. However, in the reproductive cells that give rise to eggs or sperm, each chromosome must pair with its partner. Pairing first occurs at one or more positions along each chromosome. This triggers a protein-based polymer called the “synaptonemal complex” to assemble between the paired chromosomes, and then spread along the interface between the partners until they are fully lined up side-by-side. Chromosomes in reproductive cells must pair in this particular way to exchange genetic information and generate new combinations of traits. The synaptonemal complex was first observed over 60 years ago, but it remains enigmatic. Though its structure is highly ordered and looks very similar in different organisms from yeast to humans, little is known about how this polymer forms or what it does between chromosomes. Some evidence has suggested that the synaptonemal complex helps to regulate how much information can be transferred between each pair of chromosomes, but not all studies have supported this conclusion. Several lines of evidence suggest that the synaptonemal complex might be fundamentally different from other protein-based polymers, such as those that form filamentous skeletal structures within cells, namely actin filaments and microtubules. Now, Rog et al. have tested the idea that the synaptonemal complex might actually have liquid-like properties, despite its highly ordered appearance. The experiments showed that the proteins that make up the synaptonemal complex in yeast, worms and fruit flies are weakly bound to each other and can move around within the assembled structure. These are considered to be defining properties that distinguish liquids from solid materials. Together with its regular, repetitive organization, these findings indicate that the synaptonemal complex behaves like a liquid crystal. This intriguing class of materials has properties between those of conventional liquids and those of solid crystals, and is particularly sensitive to environmental conditions. Rog et al. believe that this discovery helps to explain how signals are transmitted along the length of chromosomes to regulate the transfer of genetic information. In support of this idea, further experiments showed that proteins that are required for this recombination process were also found within the synaptonemal complex. As reproductive cells transition from one stage of their development to the next, these proteins abruptly move to a new location, indicating that a switch-like signal rapidly spreads throughout the synaptonemal complex. Together the findings suggest that the liquid crystal-like properties of the synaptonemal complex allow signals to be transmitted along the interface between pairs of chromosomes. The next challenges are to understand what triggers these signals and to explore whether they are based upon physical or chemical changes within the synaptonemal complex. Further research is also needed to uncover how this information is propagated along the length of a chromosome.

The synaptonemal complex (SC) is a meiosis-specific proteinaceous macromolecular structure that assembles between paired homologous chromosomes during meiosis in various eukaryotes. The SC has a highly conserved ultrastructure and plays critical roles in controlling multiple steps in meiotic recombination and crossover formation, ensuring accurate meiotic chromosome segregation. Recent studies in different organisms, facilitated by advances in super-resolution microscopy, have provided insights into the macromolecular structure of the SC, including the internal organization of the meiotic chromosome axis and SC central region, the regulatory pathways that control SC assembly and dynamics, and the biological functions exerted by the SC and its substructures. This review summarizes recent discoveries about how the SC is organized and regulated that help to explain the biological functions associated with this meiosis-specific structure.

Meiotic recombination plays an important role in ensuring proper chromosome segregation during meiosis I through the creation of chiasmata that connect homologous chromosomes. Recombination plays an additional role in evolution by creating new allelic combinations. Organisms display species-specific crossover patterns, but how these patterns are established is poorly understood. Drosophila mauritiana displays a different meiotic recombination pattern compared to Drosophila melanogaster , with D. mauritiana experiencing a reduced centromere effect, the suppression of recombination emanating from the centromeres. To evaluate the contribution of the synaptonemal complex (SC) C(3)G protein to these recombination rate differences, the D. melanogaster allele was replaced with D. mauritiana c(3)G coding sequence. We found that the D. mauritiana C(3)G could interact with the D. melanogaster SC machinery to build full length tripartite SC and chromosomes segregated accurately, indicating sufficient crossovers were generated. However, the placement of crossovers was altered, displaying an increase in frequency in the centromere-proximal euchromatin indicating a decrease in the centromere effect, similar to that observed in D. mauritiana females. Recovery of chromatids with more than one crossover was also increased, likely due to the larger chromosome span now available for crossovers. As replacement of a single gene mediated a strong shift of one species’ crossover pattern towards another species, it indicates a small number of discrete factors may have major influence on species-specific crossover patterning. Additionally, it demonstrates the SC, a structure known to be required for crossover formation in many species, is likely one of these discrete factors.

Meiotic recombination is essential for faithful segregation of homologous chromosomes during gametogenesis. The progression of recombination is associated with dynamic changes in meiotic chromatin structures. However, whether Sycp2, a key structural component of meiotic chromatin, is required for the initiation of meiotic recombination is still unclear in vertebrates. Here, we describe that Sycp2 is required for assembly of the synaptonemal complex and early meiotic events in zebrafish spermatocytes. Our genetic screening by N-ethyl-N-nitrosourea mutagenesis revealed that ietsugu (its), a mutant zebrafish line with an aberrant splice site in the sycp2 gene, showed a defect during meiotic prophase I. The its mutation appeared to be a hypomorphic mutation compared to sycp2 knockout mutations generated by TALEN mutagenesis. Taking advantage of these sycp2 hypomorphic and knockout mutant lines, we demonstrated that Sycp2 is required for the assembly of the synaptonemal complex that is initiated in the vicinity of telomeres in wild-type zebrafish spermatocytes. Accordingly, homologous pairing, the foci of the meiotic recombinases Dmc1/Rad51 and RPA, and γH2AX signals were largely diminished in sycp2 knockout spermatocytes. Taken together, our data indicate that Sycp2 plays a critical role in not only the assembly of the synaptonemal complex, but also early meiotic recombination and homologous pairing, in vertebrates.

A central feature of meiosis is the pairing of homologous maternal and paternal chromosomes (‘homologues’) along their lengths 1 – 3 . Recognition between homologues and their juxtaposition in space is mediated by axis-associated recombination complexes. Also, pairing must occur without entanglements among unrelated chromosomes. Here we examine homologue juxtaposition in real time by four-dimensional fluorescence imaging of tagged chromosomal loci at high spatio-temporal resolution in budding yeast. We discover that corresponding loci come together from a substantial distance (1.8 µm) and complete pairing in a very short time, about 6 min (thus, rapid homologue juxtaposition or RHJ). Homologue loci first move rapidly together (in 30 s, at speeds of roughly 60 nm s −1 ) into an intermediate stage corresponding to canonical 400 nm axis coalignment. After a short pause, crossover/non-crossover differentiation (crossover interference) mediates a second short, rapid transition that ultimately gives close pairing of axes at 100 nm by means of synaptonemal complex formation. Furthermore, RHJ (1) occurs after chromosomes acquire prophase chromosome organization, (2) is nearly synchronous over thirds of chromosome lengths, but (3) is asynchronous throughout the genome. Finally, cytoskeleton-mediated movement is important for the timing and distance of RHJ onset and for ensuring its normal progression. General implications for local and global aspects of pairing are discussed. Homologue juxtaposition during meiosis is examined in real time by imaging of tagged chromosomal loci at high resolution in budding yeast, showing that corresponding loci come together and complete pairing in a very short time.

Meiotic crossover interference is a one-dimensional spatial patterning process that produces evenly-spaced crossovers. Quantitative analysis of diagnostic molecules along budding yeast chromosomes reveals that this process sets up two interdigitated patterns, of shorter and longer periodicity, by “two-tiered” patterning. Both tiers comprise clustered assemblies of three types of molecules (“triads”) representing the three major components of meiotic chromosomes (crossover recombination, axes, and the synaptonemal complex). One tier of triads occurs at sites of majority (“canonical”) crossovers. Second tier triads are more widely spaced but also exhibit interference, dependent on the same functions as canonical crossover interference. Diverse lines of evidence suggest that second tier triads arise at sites of previously mysterious “minority” crossovers. Finally, conserved protein remodeler Pch2/TRIP13 modulates the abundance of triad components, specifically in longer periodicity triads, dynamically in real time. Potential roles of triad structure, mechanisms of two-tiered patterning, and the nature of minority crossovers are discussed. The locations of crossover recombination events along meiotic chromosomes are determined by a 1D-patterning process. Here, the authors find that this process establishes two interdigitated patterns, each composed of the same assembly of recombination proteins and chromosome structure components.

During prophase I of meiosis, chromosomes become organized as loop arrays around the proteinaceous chromosome axis. As homologous chromosomes physically pair and recombine, the chromosome axis is integrated into the tripartite synaptonemal complex (SC) as this structure’s lateral elements (LEs). While the components of the mammalian chromosome axis/LE—including meiosis-specific cohesin complexes, the axial element proteins SYCP3 and SYCP2, and the HORMA domain proteins HORMAD1 and HORMAD2—are known, the molecular organization of these components within the axis is poorly understood. Here, using expansion microscopy coupled with 2-color stochastic optical reconstruction microscopy (STORM) imaging (ExSTORM), we address these issues in mouse spermatocytes at a resolution of 10 to 20 nm. Our data show that SYCP3 and the SYCP2 C terminus, which are known to form filaments in vitro, form a compact core around which cohesin complexes, HORMADs, and the N terminus of SYCP2 are arrayed. Overall, our study provides a detailed structural view of the meiotic chromosome axis, a key organizational and regulatory component of meiotic chromosomes.