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Journal of Cell Science Sep 2015A universal feature of mitosis is that all chromosomes become aligned at the spindle equator--the halfway point between the two spindle poles--prior to anaphase onset.... (Review)
Review
A universal feature of mitosis is that all chromosomes become aligned at the spindle equator--the halfway point between the two spindle poles--prior to anaphase onset. This migratory event is called congression, and is powered by centromere-bound protein machines called kinetochores. This Commentary aims to document recent advances concerning the two kinetochore-based force-generating mechanisms that drive mitotic chromosome congression in vertebrate cells: depolymerisation-coupled pulling (DCP) and lateral sliding. We aim to explore how kinetochores can 'read-out' their spatial position within the spindle, and adjust these force-generating mechanisms to ensure chromosomes reach, and then remain, at the equator. Finally, we will describe the 'life history' of a chromosome, and provide a working model for how individual mechanisms are integrated to ensure efficient and successful congression.
Topics: Animals; Centromere; Chromosomal Puffs; Chromosome Pairing; Chromosome Segregation; HeLa Cells; Humans; Kinetochores; Models, Biological; Spindle Apparatus; Vertebrates
PubMed: 26330530
DOI: 10.1242/jcs.169367 -
Asian Journal of Andrology 2021The synaptonemal complex (SC) is a meiosis-specific proteinaceous macromolecular structure that assembles between paired homologous chromosomes during meiosis in various... (Review)
Review
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.
Topics: Animals; Chromosome Segregation; Meiosis; Synaptonemal Complex
PubMed: 34528517
DOI: 10.4103/aja202153 -
ELife Oct 2023In sexually reproducing organisms, germ cells faithfully transmit the genome to the next generation by forming haploid gametes, such as eggs and sperm. Although most...
In sexually reproducing organisms, germ cells faithfully transmit the genome to the next generation by forming haploid gametes, such as eggs and sperm. Although most meiotic proteins are conserved between eggs and sperm, many aspects of meiosis are sexually dimorphic, including the regulation of recombination. The synaptonemal complex (SC), a large ladder-like structure that forms between homologous chromosomes, is essential for regulating meiotic chromosome organization and promoting recombination. To assess whether sex-specific differences in the SC underpin sexually dimorphic aspects of meiosis, we examined SC central region proteins (known as SYP proteins) in oogenesis and spermatogenesis and uncovered sex-specific roles for the SYPs in regulating meiotic recombination. We find that SC composition, specifically SYP-2, SYP-3, SYP-5, and SYP-6, is regulated by sex-specific mechanisms throughout meiotic prophase I. During pachytene, both oocytes and spermatocytes differentially regulate the stability of SYP-2 and SYP-3 within an assembled SC. Further, we uncover that the relative amount of SYP-2 and SYP-3 within the SC is independently regulated in both a sex-specific and a recombination-dependent manner. Specifically, we find that SYP-2 regulates the early steps of recombination in both sexes, while SYP-3 controls the timing and positioning of crossover recombination events across the genomic landscape in only oocytes. Finally, we find that SYP-2 and SYP-3 dosage can influence the composition of the other SYPs in the SC via sex-specific mechanisms during pachytene. Taken together, we demonstrate dosage-dependent regulation of individual SC components with sex-specific functions in recombination. These sexual dimorphic features of the SC provide insights into how spermatogenesis and oogenesis adapted similar chromosome structures to differentially regulate and execute recombination.
Topics: Animals; Female; Male; Caenorhabditis elegans; Synaptonemal Complex; Meiosis; Semen; Caenorhabditis elegans Proteins
PubMed: 37796106
DOI: 10.7554/eLife.84538 -
Annual Review of Cell and Developmental... 2015The nervous system is populated by numerous types of neurons, each bearing a dendritic arbor with a characteristic morphology. These type-specific features influence... (Review)
Review
The nervous system is populated by numerous types of neurons, each bearing a dendritic arbor with a characteristic morphology. These type-specific features influence many aspects of a neuron's function, including the number and identity of presynaptic inputs and how inputs are integrated to determine firing properties. Here, we review the mechanisms that regulate the construction of cell type-specific dendrite patterns during development. We focus on four aspects of dendrite patterning that are particularly important in determining the function of the mature neuron: (a) dendrite shape, including branching pattern and geometry of the arbor; (b) dendritic arbor size;
Topics: Animals; Chromosome Pairing; Dendrites; Humans
PubMed: 26422333
DOI: 10.1146/annurev-cellbio-100913-013020 -
Proceedings of the National Academy of... Feb 2021Meiosis is a specialized cell division that creates haploid germ cells from diploid progenitors. Through differential RNA expression analyses, we previously identified a...
Meiosis is a specialized cell division that creates haploid germ cells from diploid progenitors. Through differential RNA expression analyses, we previously identified a number of mouse genes that were dramatically elevated in spermatocytes, relative to their very low expression in spermatogonia and somatic organs. Here, we investigated in detail one of these genes, and independently conclude that it encodes a male germline-specific protein, in agreement with a recent report. We demonstrated that it is essential for pachynema progression in spermatocytes and named it male pachynema-specific (MAPS) protein. Mice lacking ( ) suffered from pachytene arrest and spermatocyte death, leading to male infertility, whereas female fertility was not affected. Interestingly, pubertal spermatocytes were arrested at early pachytene stage, accompanied by defects in DNA double-strand break (DSB) repair, crossover formation, and XY body formation. In contrast, adult spermatocytes only exhibited partially defective crossover but nonetheless were delayed or failed in progression from early to mid- and late pachytene stage, resulting in cell death. Furthermore, we report a significant transcriptional dysregulation in autosomes and XY chromosomes in both pubertal and adult pachytene spermatocytes, including failed meiotic sex chromosome inactivation (MSCI). Further experiments revealed that MAPS overexpression in vitro dramatically decreased the ubiquitination levels of cellular proteins. Conversely, in pachytene cells, protein ubiquitination was dramatically increased, likely contributing to the large-scale disruption in gene expression in pachytene cells. Thus, MAPS is a protein essential for pachynema progression in male mice, possibly in mammals in general.
Topics: Animals; Chromosome Pairing; DNA Repair; Female; Infertility, Male; Male; Meiosis; Mice; Mice, Inbred C57BL; Mice, Knockout; Nuclear Proteins; Pachytene Stage; Sex Chromosomes; Spermatocytes; Spermatogenesis
PubMed: 33602822
DOI: 10.1073/pnas.2025421118 -
Cold Spring Harbor Perspectives in... Oct 2014The generation of haploid gametes by meiosis is a highly conserved process for sexually reproducing organisms that, in almost all cases, involves the extensive breakage... (Review)
Review
The generation of haploid gametes by meiosis is a highly conserved process for sexually reproducing organisms that, in almost all cases, involves the extensive breakage of chromosomes. These chromosome breaks occur during meiotic prophase and are essential for meiotic recombination as well as the subsequent segregation of homologous chromosomes. However, their formation and repair must be carefully monitored and choreographed with nuclear dynamics and the cell division program to avoid the creation of aberrant chromosomes and defective gametes. It is becoming increasingly clear that an intricate checkpoint-signaling network related to the canonical DNA damage response is deeply interwoven with the meiotic program and preserves order during meiotic prophase. This meiotic checkpoint network (MCN) creates a wide range of dependent relationships controlling chromosome movement, chromosome pairing, chromatin structure, and double-strand break (DSB) repair. In this review, we summarize our current understanding of the MCN. We discuss commonalities and differences in different experimental systems, with a particular emphasis on the emerging design principles that control and limit cross talk between signals to ultimately ensure the faithful inheritance of chromosomes by the next generation.
Topics: Apoptosis; Cell Cycle Checkpoints; Chromosome Pairing; DNA Breaks, Double-Stranded; DNA Repair; DNA Replication; Models, Genetic; Prophase; Recombination, Genetic; Signal Transduction
PubMed: 25274702
DOI: 10.1101/cshperspect.a016675 -
Sheng Li Xue Bao : [Acta Physiologica... Feb 2020Meiosis is a special type of cell division to produce haploid gametes with intact genome. The behavior of homologous chromosomes during the first division (meiosis... (Review)
Review
Meiosis is a special type of cell division to produce haploid gametes with intact genome. The behavior of homologous chromosomes during the first division (meiosis prophase I) is the most prominent feature of meiosis. During meiosis prophase I, synaptonemal complex (SC) formed between homologous chromosomes to promote the initiation and repair of programmed DNA double-strand breaks (DSBs), which is necessary for the correct recognition, pairing, recombination and separation of homologous chromosomes. In this paper, we reviewed the recent research progress on the composition and function of SC, discussed how the assembly of SC affected the repair of DSBs, and also summarized the known mutations on SC genes which were responsible for human reproductive disorders. On this basis, we also explored the future research direction of this field.
Topics: DNA Breaks, Double-Stranded; DNA Repair; Humans; Meiotic Prophase I; Synaptonemal Complex
PubMed: 32099986
DOI: No ID Found -
Current Topics in Developmental Biology 2023Chromosomes adopt specific conformations to regulate various cellular processes. A well-documented chromosome configuration is the highly compacted chromosome structure... (Review)
Review
Chromosomes adopt specific conformations to regulate various cellular processes. A well-documented chromosome configuration is the highly compacted chromosome structure during metaphase. More regional chromatin conformations have also been reported, including topologically associated domains encompassing mega-bases of DNA and local chromatin loops formed by kilo-bases of DNA. In this review, we discuss the changes in chromatin conformation taking place between somatic and meiotic cells, with a special focus on the establishment of a proteinaceous structure, called the chromosome axis, at the beginning of meiosis. The chromosome axis is essential to support key meiotic processes such as chromosome pairing, homologous recombination, and balanced chromosome segregation to transition from a diploid to a haploid stage. We review the role of the chromosome axis in meiotic chromatin organization and provide a detailed description of its protein composition. We also review the conserved and distinct roles between species of axis proteins in meiotic recombination, which is a major factor contributing to the creation of genetic diversity and genome evolution. Finally, we discuss situations where the chromosome axis is deregulated and evaluate the effects on genome integrity and the consequences from protein deregulation in meiocytes exposed to heat stress, and aberrant expression of genes encoding axis proteins in mammalian somatic cells associated with certain types of cancers.
Topics: Animals; Synaptonemal Complex; Meiosis; Chromosome Pairing; Chromatin; Neoplasms; Mammals
PubMed: 36681479
DOI: 10.1016/bs.ctdb.2022.04.008 -
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 -
Chromosoma Jun 2016The synaptonemal complex (SC), a key structure of meiosis that assembles during prophase I, has been initially described 60 years ago. Since then, the structure has... (Review)
Review
The synaptonemal complex (SC), a key structure of meiosis that assembles during prophase I, has been initially described 60 years ago. Since then, the structure has been described in many sexually reproducing organisms. However, the SC protein components were characterized in only few model organisms. Surprisingly, they lacked an apparent evolutionary relationship despite the conserved structural organization of the SC. For better understanding of this obvious discrepancy, the evolutionary history of the SC and its individual components has been investigated in Metazoa in detail. The results are consistent with the notion of a single origin of the metazoan SC and provide evidence for a dynamic evolutionary history of the SC components. In this mini review, we recapitulate and discuss new insights into metazoan SC evolution.
Topics: Animals; Evolution, Molecular; Humans; Synaptonemal Complex
PubMed: 26968413
DOI: 10.1007/s00412-016-0583-8