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Life Science Alliance Apr 2024Accurate centrosome separation and positioning during early mitosis relies on force-generating mechanisms regulated by a combination of extracellular, cytoplasmic, and...
Accurate centrosome separation and positioning during early mitosis relies on force-generating mechanisms regulated by a combination of extracellular, cytoplasmic, and nuclear cues. The identity of the nuclear cues involved in this process remains largely unknown. Here, we investigate how the prophase nucleus contributes to centrosome positioning during the initial stages of mitosis, using a combination of cell micropatterning, high-resolution live-cell imaging, and quantitative 3D cellular reconstruction. We show that in untransformed RPE-1 cells, centrosome positioning is regulated by a nuclear signal, independently of external cues. This nuclear mechanism relies on the linker of nucleoskeleton and cytoskeleton complex that controls the timely loading of dynein on the nuclear envelope (NE), providing spatial cues for robust centrosome positioning on the shortest nuclear axis, before nuclear envelope permeabilization. Our results demonstrate how nuclear-cytoskeletal coupling maintains a robust centrosome positioning mechanism to ensure efficient mitotic spindle assembly.
Topics: Nuclear Envelope; Centrosome; Mitosis; Prophase; Cell Nucleus
PubMed: 38228373
DOI: 10.26508/lsa.202302404 -
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 -
Annual Review of Cell and Developmental... 2008Accurate segregation of chromosomes during meiosis requires physical links between homologs. These links are usually established through chromosome pairing, synapsis,... (Review)
Review
Accurate segregation of chromosomes during meiosis requires physical links between homologs. These links are usually established through chromosome pairing, synapsis, and recombination, which occur during meiotic prophase. How chromosomes pair with their homologous partners is one of the outstanding mysteries of meiosis. Surprisingly, experimental evidence indicates that different organisms have found more than one way to accomplish this feat. Whereas some species depend on recombination machinery to achieve homologous pairing, others are able to pair and synapse their homologs in the absence of recombination. To ensure specific pairing between homologous chromosomes, both recombination-dependent and recombination-independent mechanisms must strike the proper balance between forces that promote chromosome interactions and activities that temper the promiscuity of those interactions. The initiation of synapsis is likely to be a tightly regulated step in a process that must be mechanically coupled to homolog pairing.
Topics: Animals; Centromere; Chromosome Pairing; Chromosome Segregation; Chromosomes; Meiosis; Nuclear Envelope; Recombination, Genetic; Synaptonemal Complex
PubMed: 18597662
DOI: 10.1146/annurev.cellbio.23.090506.123245 -
Journal of Molecular Cell Biology Sep 2022Meiosis is essential for evolution and genetic diversity in almost all sexual eukaryotic organisms. The mechanisms of meiotic recombination, such as synapsis, have been...
Meiosis is essential for evolution and genetic diversity in almost all sexual eukaryotic organisms. The mechanisms of meiotic recombination, such as synapsis, have been extensively investigated. However, it is still unclear whether signals from the cytoplasm or even from outside of the cell can regulate the meiosis process. Cilia are microtubule-based structures that protrude from the cell surface and function as signaling hubs to sense extracellular signals. Here, we reported an unexpected and critical role of cilia during meiotic recombination. During gametogenesis of zebrafish, cilia were specifically present in the prophase stages of both primary spermatocytes and primary oocytes. By developing a germ cell-specific CRISPR/Cas9 system, we demonstrated that germ cell-specific depletion of ciliary genes resulted in compromised double-strand break repair, reduced crossover formation, and increased germ cell apoptosis. Our study reveals a previously undiscovered role for cilia during meiosis and suggests that extracellular signals may regulate meiotic recombination via this particular organelle.
Topics: Animals; Male; Zebrafish; Cilia; Meiosis; Chromosome Pairing; DNA Repair
PubMed: 35981808
DOI: 10.1093/jmcb/mjac049 -
Nature Cell Biology Jun 2016The formation of mitotic chromosomes requires both compaction of chromatin and the resolution of replicated sister chromatids. Compaction occurs during mitotic prophase...
The formation of mitotic chromosomes requires both compaction of chromatin and the resolution of replicated sister chromatids. Compaction occurs during mitotic prophase and prometaphase, and in prophase relies on the activity of condensin II complexes. Exactly when and how sister chromatid resolution occurs has been largely unknown, as has its molecular requirements. Here, we established a method to visualize sister resolution by sequential replication labelling with two distinct nucleotide derivatives. Quantitative three-dimensional imaging then allowed us to measure the resolution of sister chromatids throughout mitosis by calculating their non-overlapping volume within the whole chromosome. Unexpectedly, we found that sister chromatid resolution starts already at the beginning of prophase, proceeds concomitantly with chromatin compaction and is largely completed by the end of prophase. Sister chromatid resolution was abolished by inhibition of topoisomerase IIα and by depleting or preventing mitotic activation of condensin II, whereas blocking cohesin dissociation from chromosomes had little effect. Mitotic sister chromatid resolution is thus an intrinsic part of mitotic chromosome formation in prophase that relies largely on DNA decatenation and shares the molecular requirement for condensin II with prophase compaction.
Topics: Adenosine Triphosphatases; Antigens, Neoplasm; Cell Line; Chromatids; DNA Replication; DNA Topoisomerases, Type II; DNA-Binding Proteins; Humans; Imaging, Three-Dimensional; Mitosis; Multiprotein Complexes; Nuclear Proteins; Prometaphase; Prophase
PubMed: 27136266
DOI: 10.1038/ncb3353 -
Annual Review of Genetics Nov 2016Comparisons among a variety of eukaryotes have revealed considerable variability in the structures and processes involved in their meiosis. Nevertheless, conventional... (Review)
Review
Comparisons among a variety of eukaryotes have revealed considerable variability in the structures and processes involved in their meiosis. Nevertheless, conventional forms of meiosis occur in all major groups of eukaryotes, including early-branching protists. This finding confirms that meiosis originated in the common ancestor of all eukaryotes and suggests that primordial meiosis may have had many characteristics in common with conventional extant meiosis. However, it is possible that the synaptonemal complex and the delicate crossover control related to its presence were later acquisitions. Later still, modifications to meiotic processes occurred within different groups of eukaryotes. Better knowledge on the spectrum of derived and uncommon forms of meiosis will improve our understanding of many still mysterious aspects of the meiotic process and help to explain the evolutionary basis of functional adaptations to the meiotic program.
Topics: Alveolata; Amoebozoa; Animals; Chromosome Pairing; Eukaryota; Fungi; Meiosis; Prophase; Recombination, Genetic; Stramenopiles; Synaptonemal Complex
PubMed: 27686280
DOI: 10.1146/annurev-genet-120215-035100 -
PLoS Genetics Apr 2023During meiotic prophase, the essential events of homolog pairing, synapsis, and recombination are coordinated with meiotic progression to promote fidelity and prevent...
During meiotic prophase, the essential events of homolog pairing, synapsis, and recombination are coordinated with meiotic progression to promote fidelity and prevent aneuploidy. The conserved AAA+ ATPase PCH-2 coordinates these events to guarantee crossover assurance and accurate chromosome segregation. How PCH-2 accomplishes this coordination is poorly understood. Here, we provide evidence that PCH-2 decelerates pairing, synapsis and recombination in C. elegans by remodeling meiotic HORMADs. We propose that PCH-2 converts the closed versions of these proteins, which drive these meiotic prophase events, to unbuckled conformations, destabilizing interhomolog interactions and delaying meiotic progression. Further, we find that PCH-2 distributes this regulation among three essential meiotic HORMADs in C. elegans: PCH-2 acts through HTP-3 to regulate pairing and synapsis, HIM-3 to promote crossover assurance, and HTP-1 to control meiotic progression. In addition to identifying a molecular mechanism for how PCH-2 regulates interhomolog interactions, our results provide a possible explanation for the expansion of the meiotic HORMAD family as a conserved evolutionary feature of meiosis. Taken together, our work demonstrates that PCH-2's remodeling of meiotic HORMADs has functional consequences for the rate and fidelity of homolog pairing, synapsis, recombination and meiotic progression, ensuring accurate meiotic chromosome segregation.
Topics: Animals; Caenorhabditis elegans; Meiosis; Adenosine Triphosphatases; Caenorhabditis elegans Proteins; Prophase; Chromosome Pairing; ATPases Associated with Diverse Cellular Activities; Cell Cycle Proteins
PubMed: 37058535
DOI: 10.1371/journal.pgen.1010708 -
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 -
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 -
Nature Mar 1957
Topics: Animals; Cell Division; Chromosomes; Female; Meiosis; Mice; Prophase
PubMed: 13418754
DOI: 10.1038/179638a0