A close-to-native structure of the synaptonemal complex

Genetic variability in sexually reproducing organisms results from an exchange of genetic material between homologous chromosomes. The genetic exchange mechanism is dependent on the synaptonemal complex (SC), a protein structure localized between the homologous chromosomes. Current structural models of the SC are based on electron microscopy, super resolution, and expansion microscopy studies using chemical fixatives and sample dehydration of gonads, which are methodologies known to produce structural artifacts. We have developed a novel electron microscopy sample-preparation approach where pachytene cells are isolated from mouse testis by FACS, followed by cryo-fixation and cryo-substitution to achieve visualization of a close-to-native structure of the SC. We found that the central region of the SC was wider than previously recognized, and the transverse filaments more densely packed in the central region. Furthermore, we identified a structure nucleating the central element of the SC.

Download Full-text

Three-Dimensional reconstruction of the synaptonemal complex from pachytene maize meiocytes using Electron Microscopy tomography

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100146758 ◽

1993 ◽

Vol 51 ◽

pp. 182-183

Author(s):

Jennifer C. Fung ◽

Bethe A. Scalettar ◽

David A. Agard ◽

John W. Sedat

Keyword(s):

Electron Microscopy ◽

Synaptonemal Complex ◽

Chromosome Segregation ◽

Three Dimensional ◽

Central Element ◽

Amorphous Structure ◽

Two Dimensional ◽

Homologous Chromosomes ◽

Exact Function ◽

Dimensional Reconstruction

The synaptonemal complex (SC) is a structure involved in the synapsis of homologous chromosomes during the prophase I stage of meiosis. Although the exact function of the complex is unknown, it has been suggested that one possible role might be to promote recombination by ensuring close synapsis of the homologous chromosomes. In addition, it is thought that the SC may also be required to convert the resulting recombination events into functional chiasmata to provide for proper chromosome segregation at the end of the first stage of meiosis.The SC structure itself is highly conserved across a variety of species. The organization of the SC is tripartite consisting of lateral, central and transverse elements. Two-dimensional cytological observations have been made to characterize the general features of these SC components. The lateral elements are 300 - 500 Å wide proteinaceous structures which flank the synapsed regions of the chromosome bivalent. Between the two lateral elements is a central region containing the central element commonly characterized as a less dense amorphous structure.

Download Full-text

Cryo-ET analysis of budding yeast synaptonemal complexes in situ

10.1101/746982 ◽

2019 ◽

Cited By ~ 2

Author(s):

Olivia X. Ma ◽

Shujun Cai ◽

Jian Shi ◽

Lu Gan

Keyword(s):

Triple Helix ◽

Phase Contrast ◽

Central Element ◽

Super Resolution ◽

Native Structure ◽

Homologous Chromosomes ◽

Triple Helices ◽

Subtomogram Averaging ◽

Electron Cryotomography

ABSTRACTThe synaptonemal complex (SC) is the large, conserved, proteinaceous scaffold that assembles between and holds together homologous chromosomes in meiotic prophase. Knowledge of the native structure of this complex is needed to evaluate how the SC carries out its functions. Traditional electron microscopy and super-resolution light microscopy have revealed that in many organisms, the SC has a ladder-like structure: two rail-like lateral elements are bridged by a set of rung-like transverse filaments. The transverse filaments are connected along their centers by a central element. To determine the 3-D architecture of the SC in situ, we studied frozen-hydrated meiotic yeast cell cryosections by Volta phase-contrast electron cryotomography and subtomogram analysis. We find the SC is built from triple-helical filaments that pack into dense polycrystalline bundles. These structures are also abundant in the polycomplexes of pachytene-arrested cells. Dissolution by 1,6-hexanediol treatment suggests that these triple-helical filaments belong to the central region of the SCs. Subtomogram averaging revealed that the SC’s triple-helical filaments are up to 12-nm thick and have a 5-nm rise and 130-nm pitch. Single triple-helices and polymers thinner than the triple helix, such as single or double strands, were not detected, consistent with the strong self-oligomerization properties of SC proteins. The dense packing of SC subunits supports the notion that the SC’s mechanical properties help coordinate the rapid end-to-end communication across synapsed chromosomes.

Download Full-text

The desynaptic mutant of maize as a combined defect of synaptonemal complex and chiasma maintenance

Genome ◽

10.1139/g91-135 ◽

1991 ◽

Vol 34 (6) ◽

pp. 879-887 ◽

Cited By ~ 24

Author(s):

M. P. Maguire ◽

A. M. Paredes ◽

R. W. Riess

Keyword(s):

Electron Microscopy ◽

Synaptonemal Complex ◽

Central Region ◽

Meiotic Prophase ◽

Heterochromatic Region ◽

Crossing Over ◽

Related Strain ◽

Normal Cells ◽

Normal Crossing ◽

Mutant Cells

The phenotype of the desynaptic (dy) mutant of maize in microsporocytes at meiotic prophase was compared with normal microsporocytes of a closely related strain and with microsporocytes of a maize inbred line (KYS) assumed to be normal. Strikingly more univalents and open arms of bivalents were found in the mutant cells than in normal cells at diakinesis, and where there was heterozygosity for a distal knob (heterochromatic region), separation was usually equational, indicating the occurrence of normal crossing-over followed by failure of chiasma maintenance in the mutant. Differences found in the mutant by electron microscopy were a statistically significant wider dimension of the synaptonemal complex central region and also less twisting of synapsed configurations at pachytene. It is suggested that these are side-effect symptoms of a defect in the synaptonemal complex (or associated substance), which is expressed later as sporadic loss of chiasma maintenance.Key words: desynaptic, chiasma maintenance, synaptonemal complex.

Download Full-text

Quantitative basis of meiotic chromosome synapsis analyzed by electron tomography

10.1101/705764 ◽

2019 ◽

Cited By ~ 2

Author(s):

Marie-Christin Spindler ◽

Sebastian Filbeck ◽

Christian Stigloher ◽

Ricardo Benavente

Keyword(s):

Central Region ◽

3D Model ◽

Electron Tomography ◽

Meiotic Chromosome ◽

Topological Analysis ◽

Central Element ◽

Morphological Data ◽

Homologous Chromosomes ◽

Chromosome Synapsis ◽

Quantitative Basis

AbstractThe synaptonemal complex is a multiprotein complex, which mediates the synapsis and recombination between homologous chromosomes during meiosis. The complex is comprised of two lateral elements and a central element connected by perpendicular transverse filaments (TFs). A 3D model based on actual morphological data of the SC is missing. Here, we applied electron tomography (ET) and manual feature extraction to generate a quantitative 3D model of the murine SC. We quantified the length (90 nm) and width (2 nm) of the TFs. Interestingly, the 80 TFs/μm are distributed asymmetrically in the central region of the SC challenging available models of SC organization. Furthermore, our detailed 3D topological analysis does not support a bilayered organization of the central region as proposed earlier. Overall, our quantitative analysis is relevant to understand the functions and dynamics of the SC and provides the basis for analyzing multiprotein complexes in their morphological context using ET.

Download Full-text

Three-Dimensional reconstruction of the synaptonemal complex from high-pressure frozen maize meiocytes using IVEM Tomography

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100167809 ◽

1994 ◽

Vol 52 ◽

pp. 14-15

Author(s):

Jennifer C. Fung ◽

David A. Agard ◽

John W. Sedat

Keyword(s):

Synaptonemal Complex ◽

Three Dimensional ◽

Central Element ◽

Homologous Chromosomes ◽

Macromolecular Assembly ◽

Dimensional Reconstruction ◽

Protein Components ◽

Basic Features ◽

General Architecture ◽

Internal Architecture

The synaptonemal complex (SC) is a key macromolecular assembly formed during meiosis of most eukaryotes. It has a crucial role in maintaining synapsis between homologous chromosomes and in ensuring proper segregation of the homologs through the establishment of functional chiasmata. Recently, biochemical and genetic efforts have begun to identify some of the protein components of the SC. As these efforts progress, a more detailed analysis of SC structure will also be needed to incorporate these new components into the overall organization of the SC.Early efforts into the analysis of SC structure have established that its general architecture is conserved throughout many organisms. The basic features found in every SC are the two lateral elements and the central element, both which run longitudinally between the homologs during the pachytene stage of prophase I. Transverse elements which run perpendicular to the homolog axis through the central region are also often found. Although the general features of the SC are conserved, the internal architecture of these components can differ.

Download Full-text

Light and electron microscope observations of a meiotic mutant of Neurospora crassa

Canadian Journal of Botany ◽

10.1139/b78-322 ◽

1978 ◽

Vol 56 (21) ◽

pp. 2694-2706 ◽

Cited By ~ 19

Author(s):

B.C. Lu ◽

Donna R. Galeazzi

Keyword(s):

Electron Microscopy ◽

Electron Microscope ◽

Genetic Analysis ◽

Neurospora Crassa ◽

Synaptonemal Complex ◽

Chromosome Pairing ◽

Light And Electron Microscopy ◽

Homologous Chromosomes ◽

Synaptonemal Complexes ◽

Nuclear Separation

Light and electron microscopy have revealed that the meiotic-1 (mei-1) mutant of Neurospora crassa is defective in chromosome pairing (asynaptic) although plenty of axial components of the synaptonemal complex are produced and occasional tripartite synaptonemal complexes can be formed. The mei-1 mutant is most probably defective in bringing the homologous chromosomes together for pairing and for assembly of the synaptonemal complex. The mei-1 mutant is also defective in nuclear separation which leads to a four-poled spindle at the subsequent division. The lack of chromosome pairing, the incomplete assembly of the synaptonemal complex, and the four-poled spindles account for absence of recombination and for the nondisjunction found in genetic analysis.

Download Full-text

PAIR3, an axis-associated protein, is essential for the recruitment of recombination elements onto meiotic chromosomes in rice

Molecular Biology of the Cell ◽

10.1091/mbc.e10-08-0667 ◽

2011 ◽

Vol 22 (1) ◽

pp. 12-19 ◽

Cited By ~ 39

Author(s):

Kejian Wang ◽

Mo Wang ◽

Ding Tang ◽

Yi Shen ◽

Baoxiang Qin ◽

...

Keyword(s):

Synaptonemal Complex ◽

Central Element ◽

Dependent Manner ◽

Homologous Pairing ◽

Homologous Chromosomes ◽

Prophase I ◽

Meiotic Chromosomes

During meiosis, the paired homologous chromosomes are tightly held together by the synaptonemal complex (SC). This complex consists of two parallel axial/lateral elements (AEs/LEs) and one central element. Here, we observed that PAIR3 localized to the chromosome core during prophase I and associated with both unsynapsed AEs and synapsed LEs. Analyses of the severe pair3 mutant demonstrated that PAIR3 was essential for bouquet formation, homologous pairing and normal recombination, and SC assembly. In addition, we showed that although PAIR3 was not required for the initial recruitment of PAIR2, it was required for the proper association of PAIR2 with chromosomes. Dual immunostaining revealed that PAIR3 highly colocalized with REC8. Moreover, studies using a rec8 mutant indicated that PAIR3 localized to chromosomes in a REC8-dependent manner.

Download Full-text

THE STRUCTURE OF THE CENTRAL REGION IN THE SYNAPTONEMAL COMPLEXES OF HAMSTER AND CRICKET SPERMATOCYTES

The Journal of Cell Biology ◽

10.1083/jcb.56.1.145 ◽

1973 ◽

Vol 56 (1) ◽

pp. 145-152 ◽

Cited By ~ 34

Author(s):

Alberto J. Solari ◽

Montrose J. Moses

Keyword(s):

Synaptonemal Complex ◽

Central Region ◽

Essential Role ◽

Amorphous Material ◽

Central Element ◽

House Cricket ◽

Widespread Occurrence ◽

Whole Mount ◽

Additional Protein ◽

Surface Spreading

The fine structure of bivalents from golden hamster and house cricket spermatocytes has been studied with a whole mount surface-spreading method combined with negative staining. The elements of the synaptonemal complex show detail of structure which is absent in other preparative procedures. The transverse filaments found in the central region of the synaptonemal complex from both species are straight and have a similar width, 1 6–1 8 nm These filaments occur mainly in bundles The central element differs in architecture in the two species In hamster bivalents it is formed of longitudinal stretches of filaments 1.6–1 8 nm wide and a small amount of an amorphous material similar to that of the lateral elements In the cricket, the central element contains transverse fibrils which are continuous with the transverse filaments of the central region, and an amorphous material lying mainly along the sides of the central element All of the components of the central region of the synaptonemal complex are resistant to pancreatic DNase. The overlapping ends of the transverse filaments, together with additional protein material, make up the central element The widespread occurrence and close morphological and histochemical interspecies similarities of the transverse filaments indicate that they serve an essential role, probably one concerned with holding synapsed bivalents together via the lateral elements. Restrictions placed by the observations reported here on current models of the synaptonemal complex are discussed.

Download Full-text

The Zip4 protein directly couples meiotic crossover formation to synaptonemal complex assembly

Genes & Development ◽

10.1101/gad.348973.121 ◽

2021 ◽

Author(s):

Alexandra Pyatnitskaya ◽

Jessica Andreani ◽

Raphaël Guérois ◽

Arnaud De Muyt ◽

Valérie Borde

Keyword(s):

Synaptonemal Complex ◽

Central Element ◽

Underlying Mechanism ◽

Double Strand Breaks ◽

General Mechanism ◽

Strand Breaks ◽

Homologous Chromosomes ◽

Evolutionarily Conserved ◽

Meiotic Crossover ◽

Chromosome Axis

Meiotic recombination is triggered by programmed double-strand breaks (DSBs), a subset of these being repaired as crossovers, promoted by eight evolutionarily conserved proteins, named ZMM. Crossover formation is functionally linked to synaptonemal complex (SC) assembly between homologous chromosomes, but the underlying mechanism is unknown. Here we show that Ecm11, a SC central element protein, localizes on both DSB sites and sites that attach chromatin loops to the chromosome axis, which are the starting points of SC formation, in a way that strictly requires the ZMM protein Zip4. Furthermore, Zip4 directly interacts with Ecm11, and point mutants that specifically abolish this interaction lose Ecm11 binding to chromosomes and exhibit defective SC assembly. This can be partially rescued by artificially tethering interaction-defective Ecm11 to Zip4. Mechanistically, this direct connection ensuring SC assembly from CO sites could be a way for the meiotic cell to shut down further DSB formation once enough recombination sites have been selected for crossovers, thereby preventing excess crossovers. Finally, the mammalian ortholog of Zip4, TEX11, also interacts with the SC central element TEX12, suggesting a general mechanism.

Download Full-text

Polo-like kinase-dependent phosphorylation of the synaptonemal complex protein SYP-4 regulates double-strand break formation through a negative feedback loop.

eLife ◽

10.7554/elife.23437 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 39

Author(s):

Saravanapriah Nadarajan ◽

Talley J Lambert ◽

Elisabeth Altendorfer ◽

Jinmin Gao ◽

Michael D Blower ◽

...

Keyword(s):

Synaptonemal Complex ◽

Central Region ◽

Feedback Loop ◽

Strand Break ◽

Dynamic State ◽

Strand Breaks ◽

Homologous Chromosomes ◽

C Elegans ◽

Complex Protein ◽

Synaptonemal Complex Protein

The synaptonemal complex (SC) is an ultrastructurally conserved proteinaceous structure that holds homologous chromosomes together and is required for the stabilization of pairing interactions and the completion of crossover (CO) formation between homologs during meiosis I. Here, we identify a novel role for a central region component of the SC, SYP-4, in negatively regulating formation of recombination-initiating double-strand breaks (DSBs) via a feedback loop triggered by crossover designation in C. elegans. We found that SYP-4 is phosphorylated dependent on Polo-like kinases PLK-1/2. SYP-4 phosphorylation depends on DSB formation and crossover designation, is required for stabilizing the SC in pachytene by switching the central region of the SC from a more dynamic to a less dynamic state, and negatively regulates DSB formation. We propose a model in which Polo-like kinases recognize crossover designation and phosphorylate SYP-4 thereby stabilizing the SC and making chromosomes less permissive for further DSB formation.

Download Full-text