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The FEBS Journal Jul 2015In meiosis, homologous chromosomes face the obstacle of finding, holding onto and segregating away from their partner chromosome. There is increasing evidence, in a... (Review)
Review
In meiosis, homologous chromosomes face the obstacle of finding, holding onto and segregating away from their partner chromosome. There is increasing evidence, in a diverse range of organisms, that centromere-centromere interactions that occur in late prophase are an important mechanism in ensuring segregation fidelity. Centromere pairing appears to initiate when homologous chromosomes synapse in meiotic prophase. Structural proteins of the synaptonemal complex have been shown to help mediate centromere pairing, but how the structure that maintains centromere pairing differs from the structure of the synaptonemal complex along the chromosomal arms remains unknown. When the synaptonemal complex proteins disassemble from the chromosome arms in late prophase, some of these synaptonemal complex components persist at the centromeres. In yeast and Drosophila these centromere-pairing behaviors promote the proper segregation of chromosome partners that have failed to become linked by chiasmata. Recent studies of mouse spermatocytes have described centromere pairing behaviors that are similar in several respects to what has been described in the fly and yeast systems. In humans, chromosomes that fail to experience crossovers in meiosis are error-prone and are a major source of aneuploidy. The finding that centromere pairing is a conserved phenomenon raises the possibility that it may play a role in promoting the segregation fidelity of non-exchange chromosome pairs in humans.
Topics: Animals; Centromere; Chromosome Pairing; Chromosome Segregation; Humans; Meiosis; Synaptonemal Complex
PubMed: 25817724
DOI: 10.1111/febs.13280 -
Cellular and Molecular Life Sciences :... Nov 2003Telomeres carry out conserved and possibly ancient functions in meiosis. During the specialized prophase of meiosis I, meiotic prophase, telomeres cluster on the nuclear... (Review)
Review
Telomeres carry out conserved and possibly ancient functions in meiosis. During the specialized prophase of meiosis I, meiotic prophase, telomeres cluster on the nuclear envelope and move the diploid genetic material around within the nucleus so that homologous chromosomes can align two by two and efficiently recombine with precision. This recombination is in turn required for proper segregation of the homologs into viable haploid daughter cells. The meiosis-specific telomere clustering on the nuclear envelope defines the bouquet stage, so named for its resemblance to the stems from a bouquet of cut flowers. Here, a comparative analysis of the literature on meiotic telomeres from a variety of different species illustrates that the bouquet is nearly universal among life cycles with sexual reproduction. The bouquet has been well documented for over 100 years, but our understanding of how it forms and how it functions has only recently begun to increase. Early and recent observations document the timing and provide clues about the functional significance of these striking telomere movements.
Topics: Animals; DNA; Humans; Meiosis; Nuclear Envelope; Prophase; Telomere
PubMed: 14625678
DOI: 10.1007/s00018-003-3312-4 -
Annual Review of Genetics Nov 2016Meiosis, the mechanism of creating haploid gametes, is a complex cellular process observed across sexually reproducing organisms. Fundamental to meiosis is the process... (Review)
Review
Meiosis, the mechanism of creating haploid gametes, is a complex cellular process observed across sexually reproducing organisms. Fundamental to meiosis is the process of homologous recombination, whereby DNA double-strand breaks are introduced into the genome and are subsequently repaired to generate either noncrossovers or crossovers. Although homologous recombination is essential for chromosome pairing during prophase I, the resulting crossovers are critical for maintaining homolog interactions and enabling accurate segregation at the first meiotic division. Thus, the placement, timing, and frequency of crossover formation must be exquisitely controlled. In this review, we discuss the proteins involved in crossover formation, the process of their formation and designation, and the rules governing crossovers, all within the context of the important landmarks of prophase I. We draw together crossover designation data across organisms, analyze their evolutionary divergence, and propose a universal model for crossover regulation.
Topics: Aneuploidy; Animals; Crossing Over, Genetic; DNA Breaks, Double-Stranded; DNA Repair; Meiosis; Meiotic Prophase I; Protein Processing, Post-Translational; Recombination, Genetic; Synaptonemal Complex
PubMed: 27648641
DOI: 10.1146/annurev-genet-120215-035111 -
ELife Jan 2021Protein modification by SUMO helps orchestrate the elaborate events of meiosis to faithfully produce haploid gametes. To date, only a handful of meiotic SUMO targets...
Protein modification by SUMO helps orchestrate the elaborate events of meiosis to faithfully produce haploid gametes. To date, only a handful of meiotic SUMO targets have been identified. Here, we delineate a multidimensional SUMO-modified meiotic proteome in budding yeast, identifying 2747 conjugation sites in 775 targets, and defining their relative levels and dynamics. Modified sites cluster in disordered regions and only a minority match consensus motifs. Target identities and modification dynamics imply that SUMOylation regulates all levels of chromosome organization and each step of meiotic prophase I. Execution-point analysis confirms these inferences, revealing functions for SUMO in S-phase, the initiation of recombination, chromosome synapsis and crossing over. K15-linked SUMO chains become prominent as chromosomes synapse and recombine, consistent with roles in these processes. SUMO also modifies ubiquitin, forming hybrid oligomers with potential to modulate ubiquitin signaling. We conclude that SUMO plays diverse and unanticipated roles in regulating meiotic chromosome metabolism.
Topics: Chromosome Pairing; Meiosis; Prophase; SUMO-1 Protein; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Sumoylation
PubMed: 33502312
DOI: 10.7554/eLife.57720 -
Current Topics in Developmental Biology 2023Sexual reproduction and the specialized cell division it relies upon, meiosis, are biological processes that present an incredible degree of both evolutionary... (Review)
Review
Sexual reproduction and the specialized cell division it relies upon, meiosis, are biological processes that present an incredible degree of both evolutionary conservation and divergence. One clear example of this paradox is the role of the evolutionarily ancient PCH-2/HORMAD module during meiosis. On one hand, the complex, and sometimes disparate, meiotic defects observed when PCH-2 and/or the meiotic HORMADS are mutated in different model systems have prevented a straightforward characterization of their conserved functions. On the other hand, these functional variations demonstrate the impressive molecular rewiring that accompanies evolution of the meiotic processes these factors are involved in. While the defects observed in pch-2 mutants appear to vary in different systems, in this review, I argue that PCH-2 has a conserved meiotic function: to coordinate meiotic recombination with synapsis to ensure an appropriate number and distribution of crossovers. Further, given the dramatic variation in how the events of recombination and synapsis are themselves regulated in different model systems, the mechanistic differences in PCH-2 and meiotic HORMAD function make biological sense when viewed as species-specific elaborations layered onto this fundamental, conserved role.
Topics: Adenosine Triphosphatases; Meiosis; Chromosome Pairing
PubMed: 36681475
DOI: 10.1016/bs.ctdb.2022.07.001 -
Molecular Biology of the Cell May 2022Homologous recombination (HR) is an essential meiotic process that contributes to the genetic variation of offspring and ensures accurate chromosome segregation....
Homologous recombination (HR) is an essential meiotic process that contributes to the genetic variation of offspring and ensures accurate chromosome segregation. Recombination is facilitated by the formation and repair of programmed DNA double-strand breaks. These DNA breaks are repaired via recombination between maternal and paternal homologous chromosomes and a subset result in the formation of crossovers. HR and crossover formation is facilitated by synapsis of homologous chromosomes by a proteinaceous scaffold structure known as the synaptonemal complex (SC). Recent studies in yeast and worms have indicated that polo-like kinases (PLKs) regulate several events during meiosis, including DNA recombination and SC dynamics. Mammals express four active PLKs (PLK1-4), and our previous work assessing localization and kinase function in mouse spermatocytes suggested that PLK1 coordinates nuclear events during meiotic prophase. Therefore, we conditionally mutated in early prophase spermatocytes and assessed stages of HR, crossover formation, and SC processes. mutation resulted in increased RPA foci and reduced RAD51/DMC1 foci during zygonema, and an increase of both class I and class II crossover events. Furthermore, the disassembly of SC lateral elements was aberrant. Our results highlight the importance of PLK1 in regulating HR and SC disassembly during spermatogenesis.
Topics: Animals; Cell Cycle Proteins; Chromosome Pairing; DNA; Homologous Recombination; Male; Mammals; Meiosis; Mice; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Spermatogenesis; Synaptonemal Complex; Polo-Like Kinase 1
PubMed: 35274968
DOI: 10.1091/mbc.E21-03-0115 -
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 -
Science Advances Oct 2023In almost all sexually reproducing organisms, meiotic recombination and cell division require the synapsis of homologous chromosomes by a large proteinaceous structure,...
In almost all sexually reproducing organisms, meiotic recombination and cell division require the synapsis of homologous chromosomes by a large proteinaceous structure, the synaptonemal complex (SC). While the SC's overall structure is highly conserved across eukaryotes, its constituent proteins diverge between phyla. Transverse filament protein, SYCP1, spans the width of the SC and undergoes amino-terminal head-to-head self-assembly in vitro through a motif that is unusually highly conserved across kingdoms of life. Here, we report creation of mouse mutants, and , that target SYCP1's head-to-head interface. L106E resulted in a complete loss of synapsis, while L102E had no apparent effect on synapsis, in agreement with their differential effects on the SYCP1 head-to-head interface in molecular dynamics simulations. In mice, homologs aligned and recruited low levels of mutant SYCP1 and other SC proteins, but the absence of synapsis led to failure of crossover formation and meiotic arrest. We conclude that SYCP1's conserved head-to-head interface is essential for meiotic chromosome synapsis in vivo.
Topics: Animals; Mice; Chromosome Pairing; Homologous Recombination; Meiosis; Nuclear Proteins; Synaptonemal Complex
PubMed: 37862414
DOI: 10.1126/sciadv.adi1562 -
Genes & Development Dec 2020Proper segregation during meiosis requires that homologs be connected by the combination of crossovers and sister chromatid cohesion. To generate crossovers, numerous... (Review)
Review
Proper segregation during meiosis requires that homologs be connected by the combination of crossovers and sister chromatid cohesion. To generate crossovers, numerous double-strand breaks (DSBs) are introduced throughout the genome by the conserved Spo11 endonuclease. DSB formation and its repair are then highly regulated to ensure that homologous chromosomes contain at least one crossover and no DSBs remain prior to meiosis I segregation. The synaptonemal complex (SC) is a meiosis-specific structure formed between homologous chromosomes during prophase that promotes DSB formation and biases repair of DSBs to homologs over sister chromatids. Synapsis occurs when a particular recombination pathway is successful in establishing stable interhomolog connections. In this issue of , Mu and colleagues (pp. 1605-1618) show that SC formation between individual chromosomes provides the feedback to down-regulate Spo11 activity, thereby revealing an additional function for the SC.
Topics: Chromatids; DNA Breaks, Double-Stranded; Homologous Recombination; Meiosis; Synaptonemal Complex
PubMed: 33262143
DOI: 10.1101/gad.345488.120 -
Cell Cycle (Georgetown, Tex.) 2015During meiotic prophase, DNA double-strand break (DSB) repair-mediated homologous recombination (HR) occurs for exchange of genetic information between homologous... (Review)
Review
During meiotic prophase, DNA double-strand break (DSB) repair-mediated homologous recombination (HR) occurs for exchange of genetic information between homologous chromosomes. Unlike autosomes or female sex chromosomes, human male sex chromosomes X and Y share little homology. Although DSBs are generated throughout male sex chromosomes, homologous recombination does not occur for most regions and DSB repair process is significantly prolonged. As a result, male sex chromosomes are coated with many DNA damage response proteins and form a unique chromatin structure known as the XY body. Interestingly, associated with the prolonged DSB repair, transcription is repressed in the XY body but not in autosomes, a phenomenon known as meiotic sex chromosome inactivation (MSCI), which is critical for male meiosis. Here using mice as model organisms, we briefly summarize recent progress on DSB repair in meiotic prophase and focus on the mechanism and function of DNA damage response in the XY body.
Topics: Animals; Carrier Proteins; Crossing Over, Genetic; DNA Breaks, Double-Stranded; DNA Repair; Male; Mice; Models, Biological; Prophase; Sex Chromosomes; Ubiquitin-Protein Ligases
PubMed: 25565522
DOI: 10.1080/15384101.2014.998070