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Cellular and Molecular Life Sciences :... Apr 2009Meiosis is a key cellular and molecular process for sexual reproduction contributing to the genetic variability of organisms. This process takes place after DNA... (Review)
Review
Meiosis is a key cellular and molecular process for sexual reproduction contributing to the genetic variability of organisms. This process takes place after DNA replication and consists in a double cellular division, giving rise to four haploid daughter cells or gametes. Meiotic recombination between homologous chromosomes, in the meiotic prophase I, is mediated by a tripartite structure named Synaptonemal Complex (SC). The SC is a peptidic scaffold in which the chromatin of homologous chromosomes is organized during the pachytene stage, holding chromosomes together until the meiotic recombination and genetic exchange have taken place. The role of chromatin structure in formation of the SC and the meiotic recombination at meiotic prophase I remain largely unknown. In this review we address the epigenome contribution to the SC formation at meiotic prophase I, with particular attention on the chromatin structure modifications occurring during the sub-stages of meiotic prophase I.
Topics: Animals; Chromatin; Chromosomes; DNA Methylation; DNA Replication; Epigenesis, Genetic; Meiosis; Meiotic Prophase I; Recombination, Genetic; Synaptonemal Complex
PubMed: 19099188
DOI: 10.1007/s00018-008-8584-2 -
Cancer Science Mar 2021The synaptonemal complex (SC) is a proteinaceous structure that is transiently formed during meiosis to promote homologous recombination between maternal and paternal... (Review)
Review
The synaptonemal complex (SC) is a proteinaceous structure that is transiently formed during meiosis to promote homologous recombination between maternal and paternal chromosomes. As this structure is required only for meiotic recombination, the proteins constituting the complex are almost undetectable in normal somatic cells, but they can be expressed under the conditions in which the transcriptional machinery is deregulated. Accumulating evidence indicates that they are epigenetically expressed in cancers of various origin. Not surprisingly, in contrast to their meiotic roles, the somatic roles of the SC proteins remain to be investigated. However, it has recently been reported that SYCP3 and SYCE2 control DNA double-strand break repair negatively and positively, respectively, suggesting that the ectopic expression of the SC proteins in somatic cells could be associated with the maintenance of genomic instability. Thus, it is highly likely that the investigation of the somatic roles of the SC proteins would improve our understanding of the mechanisms underlying tumor development.
Topics: Animals; Cell Cycle Proteins; DNA Breaks, Double-Stranded; DNA-Binding Proteins; Epigenesis, Genetic; Genomic Instability; Humans; Mice; Models, Animal; Neoplasms; Nuclear Proteins; Recombinational DNA Repair; Synaptonemal Complex
PubMed: 33382503
DOI: 10.1111/cas.14791 -
PLoS Genetics Mar 2021During sexual reproduction the parental homologous chromosomes find each other (pair) and align along their lengths by integrating local sequence homology with...
During sexual reproduction the parental homologous chromosomes find each other (pair) and align along their lengths by integrating local sequence homology with large-scale contiguity, thereby allowing for precise exchange of genetic information. The Synaptonemal Complex (SC) is a conserved zipper-like structure that assembles between the homologous chromosomes, bringing them together and regulating exchanges between them. However, the molecular mechanisms by which the SC carries out these functions remain poorly understood. Here we isolated and characterized two mutations in the dimerization interface in the middle of the SC zipper in C. elegans. The mutations perturb both chromosome alignment and the regulation of genetic exchanges. Underlying the chromosome-scale phenotypes are distinct alterations to the way SC subunits interact with one another. We propose a model whereby the SC brings homologous chromosomes together through two activities: obligate zipping that prevents assembly on unpaired chromosomes; and a tendency to extend pairing interactions along the entire length of the chromosomes.
Topics: Amino Acid Sequence; Animals; Caenorhabditis elegans Proteins; Chromosome Pairing; Crossing Over, Genetic; Fluorescent Antibody Technique; Immunohistochemistry; Male; Meiosis; Mutation; Nuclear Proteins; Protein Binding; Protein Interaction Domains and Motifs; Synaptonemal Complex
PubMed: 33730019
DOI: 10.1371/journal.pgen.1009205 -
Philosophical Transactions of the Royal... Dec 2017Meiosis is unusual among cell divisions in shuffling genetic material by crossovers among homologous chromosomes and partitioning the genome into haploid gametes.... (Review)
Review
Meiosis is unusual among cell divisions in shuffling genetic material by crossovers among homologous chromosomes and partitioning the genome into haploid gametes. Crossovers are critical for chromosome segregation in most eukaryotes, but are also an important factor in evolution, as they generate novel genetic combinations. The molecular mechanisms that underpin meiotic recombination and chromosome segregation are well conserved across kingdoms, but are also sensitive to perturbation by environment, especially temperature. Even subtle shifts in temperature can alter the number and placement of crossovers, while at greater extremes, structural failures can occur in the linear axis and synaptonemal complex structures which are essential for recombination and chromosome segregation. Understanding the effects of temperature on these processes is important for its implications in evolution and breeding, especially in the context of global warming. In this review, we first summarize the process of meiotic recombination and its reliance on axis and synaptonemal complex structures, and then discuss effects of temperature on these processes and structures. We hypothesize that some consistent effects of temperature on recombination and meiotic thermotolerance may commonly be two sides of the same coin, driven by effects of temperature on the folding or interaction of key meiotic proteins.This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'.
Topics: Global Warming; Meiosis; Recombination, Genetic; Synaptonemal Complex; Temperature; Thermotolerance
PubMed: 29109229
DOI: 10.1098/rstb.2016.0470 -
Nature Communications Oct 2022Meiotic crossovers are limited in number and are prevented from occurring close to each other by crossover interference. In many species, crossover number is subject to...
Meiotic crossovers are limited in number and are prevented from occurring close to each other by crossover interference. In many species, crossover number is subject to sexual dimorphism, and a lower crossover number is associated with shorter chromosome axes lengths. How this patterning is imposed remains poorly understood. Here, we show that overexpression of the Arabidopsis pro-crossover protein HEI10 increases crossovers but maintains some interference and sexual dimorphism. Disrupting the synaptonemal complex by mutating ZYP1 also leads to an increase in crossovers but, in contrast, abolishes interference and disrupts the link between chromosome axis length and crossovers. Crucially, combining HEI10 overexpression and zyp1 mutation leads to a massive and unprecedented increase in crossovers. These observations support and can be predicted by, a recently proposed model in which HEI10 diffusion along the synaptonemal complex drives a coarsening process leading to well-spaced crossover-promoting foci, providing a mechanism for crossover patterning.
Topics: Arabidopsis; Arabidopsis Proteins; Chromosomal Proteins, Non-Histone; Crossing Over, Genetic; Meiosis; Synaptonemal Complex
PubMed: 36224180
DOI: 10.1038/s41467-022-33472-w -
PLoS Genetics Jul 2023The successful delivery of genetic material to gametes requires tightly regulated interactions between the parental chromosomes. Central to this regulation is a... (Review)
Review
The successful delivery of genetic material to gametes requires tightly regulated interactions between the parental chromosomes. Central to this regulation is a conserved chromosomal interface called the synaptonemal complex (SC), which brings the parental chromosomes in close proximity along their length. While many of its components are known, the interfaces that mediate the assembly of the SC remain a mystery. Here, we survey findings from different model systems while focusing on insight gained in the nematode C. elegans. We synthesize our current understanding of the structure, dynamics, and biophysical properties of the SC and propose mechanisms for SC assembly.
Topics: Animals; Synaptonemal Complex; Caenorhabditis elegans; Meiosis; Chromosome Pairing; Caenorhabditis elegans Proteins
PubMed: 37471284
DOI: 10.1371/journal.pgen.1010822 -
Open Biology May 2021Chromosome segregation in eukaryotes is driven by the kinetochore, a macromolecular complex that connects centromeric DNA to microtubules of the spindle apparatus....
Chromosome segregation in eukaryotes is driven by the kinetochore, a macromolecular complex that connects centromeric DNA to microtubules of the spindle apparatus. Kinetochores in well-studied model eukaryotes consist of a core set of proteins that are broadly conserved among distant eukaryotic phyla. By contrast, unicellular flagellates of the class Kinetoplastida have a unique set of 36 kinetochore components. The evolutionary origin and history of these kinetochores remain unknown. Here, we report evidence of homology between axial element components of the synaptonemal complex and three kinetoplastid kinetochore proteins KKT16-18. The synaptonemal complex is a zipper-like structure that assembles between homologous chromosomes during meiosis to promote recombination. By using sensitive homology detection protocols, we identify divergent orthologues of KKT16-18 in most eukaryotic supergroups, including experimentally established chromosomal axis components, such as Red1 and Rec10 in budding and fission yeast, ASY3-4 in plants and SYCP2-3 in vertebrates. Furthermore, we found 12 recurrent duplications within this ancient eukaryotic SYCP gene family, providing opportunities for new functional complexes to arise, including KKT16-18 in the kinetoplastid parasite . We propose the kinetoplastid kinetochore system evolved by repurposing meiotic components of the chromosome synapsis and homologous recombination machinery that were already present in early eukaryotes.
Topics: Chromosome Segregation; Kinetochores; Protozoan Proteins; Synaptonemal Complex; Trypanosoma brucei brucei
PubMed: 34006126
DOI: 10.1098/rsob.210049 -
American Journal of Human Genetics Feb 2021Human infertility is a multifactorial disease that affects 8%-12% of reproductive-aged couples worldwide. However, the genetic causes of human infertility are still...
Human infertility is a multifactorial disease that affects 8%-12% of reproductive-aged couples worldwide. However, the genetic causes of human infertility are still poorly understood. Synaptonemal complex (SC) is a conserved tripartite structure that holds homologous chromosomes together and plays an indispensable role in the meiotic progression. Here, we identified three homozygous mutations in the SC coding gene C14orf39/SIX6OS1 in infertile individuals from different ethnic populations by whole-exome sequencing (WES). These mutations include a frameshift mutation (c.204_205del [p.His68Glnfs2]) from a consanguineous Pakistani family with two males suffering from non-obstructive azoospermia (NOA) and one female diagnosed with premature ovarian insufficiency (POI) as well as a nonsense mutation (c.958G>T [p.Glu320]) and a splicing mutation (c.1180-3C>G) in two unrelated Chinese men (individual P3907 and individual P6032, respectively) with meiotic arrest. Mutations in C14orf39 resulted in truncated proteins that retained SYCE1 binding but exhibited impaired polycomplex formation between C14ORF39 and SYCE1. Further cytological analyses of meiosis in germ cells revealed that the affected familial males with the C14orf39 frameshift mutation displayed complete asynapsis between homologous chromosomes, while the affected Chinese men carrying the nonsense or splicing mutation showed incomplete synapsis. The phenotypes of NOA and POI in affected individuals were well recapitulated by Six6os1 mutant mice carrying an analogous mutation. Collectively, our findings in humans and mice highlight the conserved role of C14ORF39/SIX6OS1 in SC assembly and indicate that the homozygous mutations in C14orf39/SIX6OS1 described here are responsible for infertility of these affected individuals, thus expanding our understanding of the genetic basis of human infertility.
Topics: Adult; Azoospermia; Chromosome Pairing; Codon, Nonsense; DNA-Binding Proteins; Female; Homozygote; Humans; Male; Meiosis; Middle Aged; Mutation; Nuclear Proteins; Pedigree; Primary Ovarian Insufficiency; Spermatocytes; Synaptonemal Complex; Whole Genome Sequencing
PubMed: 33508233
DOI: 10.1016/j.ajhg.2021.01.010 -
Cytogenetic and Genome Research 2016Human infertility is often classified as idiopathic in both males and females. Meiotic errors may account for at least part of these cases. As the synaptonemal complex... (Review)
Review
Human infertility is often classified as idiopathic in both males and females. Meiotic errors may account for at least part of these cases. As the synaptonemal complex (SC, a meiosis-specific protein scaffold) is essential for successful meiosis progression, in this paper, we analyzed the mutations in genes coding for SC components described in infertile patients to assess to what extent alterations in the SC can be related to human infertility. So far, mutations in SYCP3 and SYCE1 genes have been reported. While most SYCP3 mutations are heterozygous mutations with dominant-negative effect on the region encoding the C-terminal coiled coil of the protein, SYCE1 mutations are homozygous, which is consistent with a recessive inheritance. Similarities and differences between males and females as well as between mice and humans have been found and are discussed herein. The results suggest that a low percentage of human infertility cases may be explained by mutations in genes coding for SC components. The characterization of these mutations, together with available information from the study of knockout mice, will enable a deeper understanding of the underlying molecular bases for some of the cases of idiopathic infertility.
Topics: Animals; Cell Cycle Proteins; Chromosomal Proteins, Non-Histone; DNA-Binding Proteins; Female; Fertility; Humans; Male; Mice; Mice, Knockout; Mutation; Nuclear Proteins; Synaptonemal Complex
PubMed: 27997882
DOI: 10.1159/000453344 -
Genetics Mar 2018A century of genetic studies of the meiotic process in females has been greatly augmented by both modern molecular biology and major advances in cytology. These... (Review)
Review
A century of genetic studies of the meiotic process in females has been greatly augmented by both modern molecular biology and major advances in cytology. These approaches, and the findings they have allowed, are the subject of this review. Specifically, these efforts have revealed that meiotic pairing in females is not an extension of somatic pairing, but rather occurs by a poorly understood process during premeiotic mitoses. This process of meiotic pairing requires the function of several components of the synaptonemal complex (SC). When fully assembled, the SC also plays a critical role in maintaining homolog synapsis and in facilitating the maturation of double-strand breaks (DSBs) into mature crossover (CO) events. Considerable progress has been made in elucidating not only the structure, function, and assembly of the SC, but also the proteins that facilitate the formation and repair of DSBs into both COs and noncrossovers (NCOs). The events that control the decision to mature a DSB as either a CO or an NCO, as well as determining which of the two CO pathways (class I or class II) might be employed, are also being characterized by genetic and genomic approaches. These advances allow a reconsideration of meiotic phenomena such as interference and the centromere effect, which were previously described only by genetic studies. In delineating the mechanisms by which the oocyte controls the number and position of COs, it becomes possible to understand the role of CO position in ensuring the proper orientation of homologs on the first meiotic spindle. Studies of bivalent orientation have occurred in the context of numerous investigations into the assembly, structure, and function of the first meiotic spindle. Additionally, studies have examined the mechanisms ensuring the segregation of chromosomes that have failed to undergo crossing over.
Topics: Animals; Centromere; Chromosome Painting; Chromosome Pairing; Chromosome Segregation; Crossing Over, Genetic; DNA Breaks, Double-Stranded; Drosophila melanogaster; Female; Meiosis; Oocytes; Recombination, Genetic; Spindle Apparatus; Synaptonemal Complex
PubMed: 29487146
DOI: 10.1534/genetics.117.300081