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Cells Nov 2022Aneuploidy is a hallmark of cancer and a major cause of miscarriages in humans. It is caused by chromosome segregation errors during cell divisions. Evidence is mounting... (Review)
Review
Aneuploidy is a hallmark of cancer and a major cause of miscarriages in humans. It is caused by chromosome segregation errors during cell divisions. Evidence is mounting that the probability of specific chromosomes undergoing a segregation error is non-random. In other words, some chromosomes have a higher chance of contributing to aneuploid karyotypes than others. This could have important implications for the origins of recurrent aneuploidy patterns in cancer and developing embryos. Here, we review recent progress in understanding the prevalence and causes of non-random chromosome segregation errors in mammalian mitosis and meiosis. We evaluate its potential impact on cancer and human reproduction and discuss possible research avenues.
Topics: Animals; Humans; Meiosis; Mitosis; Chromosomes; Chromosome Segregation; Aneuploidy; Mammals
PubMed: 36428993
DOI: 10.3390/cells11223564 -
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 -
BMC Biology Mar 2023Ovarian folliculogenesis is a tightly regulated process leading to the formation of functional oocytes and involving successive quality control mechanisms that monitor...
BACKGROUND
Ovarian folliculogenesis is a tightly regulated process leading to the formation of functional oocytes and involving successive quality control mechanisms that monitor chromosomal DNA integrity and meiotic recombination. A number of factors and mechanisms have been suggested to be involved in folliculogenesis and associated with premature ovarian insufficiency, including abnormal alternative splicing (AS) of pre-mRNAs. Serine/arginine-rich splicing factor 1 (SRSF1; previously SF2/ASF) is a pivotal posttranscriptional regulator of gene expression in various biological processes. However, the physiological roles and mechanism of SRSF1 action in mouse early-stage oocytes remain elusive. Here, we show that SRSF1 is essential for primordial follicle formation and number determination during meiotic prophase I.
RESULTS
The conditional knockout (cKO) of Srsf1 in mouse oocytes impairs primordial follicle formation and leads to primary ovarian insufficiency (POI). Oocyte-specific genes that regulate primordial follicle formation (e.g., Lhx8, Nobox, Sohlh1, Sohlh2, Figla, Kit, Jag1, and Rac1) are suppressed in newborn Stra8-GFPCre Srsf1 mouse ovaries. However, meiotic defects are the leading cause of abnormal primordial follicle formation. Immunofluorescence analyses suggest that failed synapsis and an inability to undergo recombination result in fewer homologous DNA crossovers (COs) in the Srsf1 cKO mouse ovaries. Moreover, SRSF1 directly binds and regulates the expression of the POI-related genes Six6os1 and Msh5 via AS to implement the meiotic prophase I program.
CONCLUSIONS
Altogether, our data reveal the critical role of an SRSF1-mediated posttranscriptional regulatory mechanism in the mouse oocyte meiotic prophase I program, providing a framework to elucidate the molecular mechanisms of the posttranscriptional network underlying primordial follicle formation.
Topics: Animals; Female; Mice; Alternative Splicing; Cell Cycle Proteins; DNA-Binding Proteins; Meiosis; Meiotic Prophase I; Oocytes; Ovary; Serine-Arginine Splicing Factors
PubMed: 36882745
DOI: 10.1186/s12915-023-01549-7 -
Current Genetics Aug 2019Sister chromatid cohesion is essential for chromosome segregation both in mitosis and meiosis. Cohesion between two chromatids is mediated by a protein complex called... (Review)
Review
Sister chromatid cohesion is essential for chromosome segregation both in mitosis and meiosis. Cohesion between two chromatids is mediated by a protein complex called cohesin. The loading and unloading of the cohesin are tightly regulated during the cell cycle. In vertebrate cells, cohesin is released from chromosomes by two distinct pathways. The best characterized pathway occurs at the onset of anaphase, when the kleisin component of the cohesin is destroyed by a protease, separase. The cleavage of the cohesin by separase releases entrapped sister chromatids allowing anaphase to commence. In addition, prior to the metaphase-anaphase transition, most of cohesin is removed from chromosomes in a cleavage-independent manner. This cohesin release is referred to as the prophase pathway. In meiotic cells, sister chromatid cohesion is essential for the segregation of homologous chromosomes during meiosis I. Thus, it was assumed that the prophase pathway for cohesin removal from chromosome arms would be suppressed during meiosis to avoid errors in chromosome segregation. However, recent studies revealed the presence of a meiosis-specific prophase-like pathway for cleavage-independent removal of cohesin during late prophase I in different organisms. In budding yeast, the cleavage-independent removal of cohesin is mediated through meiosis-specific phosphorylation of cohesin subunits, Rec8, the meiosis-specific kleisin, and the yeast Wapl ortholog, Rad61/Wpl1. This pathway plays a role in chromosome morphogenesis during late prophase I, promoting chromosome compaction. In this review, we give an overview of the prophase pathway for cohesin dynamics during meiosis, which has a complex regulation leading to differentially localized populations of cohesin along meiotic chromosomes.
Topics: Anaphase; Cell Cycle Proteins; Chromatids; Chromosomal Proteins, Non-Histone; Chromosome Segregation; Meiosis; Metaphase; Morphogenesis; Prophase; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Cohesins
PubMed: 30923890
DOI: 10.1007/s00294-019-00959-x -
Seminars in Cell & Developmental Biology Aug 2022Despite the universal requirement for faithful chromosome segregation, eukaryotic centromeres are rapidly evolving. It is hypothesized that rapid centromere evolution... (Review)
Review
Despite the universal requirement for faithful chromosome segregation, eukaryotic centromeres are rapidly evolving. It is hypothesized that rapid centromere evolution represents an evolutionary arms race between selfish genetic elements that drive, or propagate at the expense of organismal fitness, and mechanisms that suppress fitness costs. Selfish centromere DNA achieves preferential inheritance in female meiosis by recruiting more effector proteins that alter spindle microtubule interaction dynamics. Parallel pathways for effector recruitment are adaptively evolved to suppress functional differences between centromeres. Opportunities to drive are not limited to female meiosis, and selfish transposons, plasmids and B chromosomes also benefit by maximizing their inheritance. Rapid evolution of selfish genetic elements can diversify suppressor mechanisms in different species that may cause hybrid incompatibility.
Topics: Centromere; Chromosome Segregation; Eukaryota; Female; Humans; Meiosis; Microtubules
PubMed: 35346579
DOI: 10.1016/j.semcdb.2022.03.026 -
Cell Jun 2020Meiosis is the specialized cell division that generates haploid gametes and is therefore essential for sexual reproduction. This SnapShot encompasses key events taking...
Meiosis is the specialized cell division that generates haploid gametes and is therefore essential for sexual reproduction. This SnapShot encompasses key events taking place during prophase I of meiosis that are required for achieving proper chromosome segregation and highlights how these are both conserved and diverged throughout five different species. To view this SnapShot, open or download the PDF.
Topics: Animals; Arabidopsis; Caenorhabditis elegans; Chromosome Segregation; Drosophila melanogaster; Meiosis; Meiotic Prophase I; Mice; Saccharomyces cerevisiae
PubMed: 32531249
DOI: 10.1016/j.cell.2020.04.038 -
Current Topics in Developmental Biology 2023Meiosis increases genetic diversity in offspring by generating genetically unique haploid gametes with reshuffled chromosomes. This process requires a specialized set of... (Review)
Review
Meiosis increases genetic diversity in offspring by generating genetically unique haploid gametes with reshuffled chromosomes. This process requires a specialized set of meiotic proteins, which facilitate chromosome recombination and segregation. However, re-expression of meiotic proteins in mitosis can have catastrophic oncogenic consequences and aberrant expression of meiotic proteins is a common occurrence in human tumors. Mechanistically, re-activation of meiotic genes in cancer promotes oncogenesis likely because cancers-conversely to healthy mitosis-are fueled by genetic instability which promotes tumor evolution, and evasion of immune response and treatment pressure. In this review, we explore similarities between meiotic and cancer cells with a particular focus on the oncogenic activation of meiotic genes in cancer. We emphasize the role of histones and their modifications, DNA methylation, genome organization, R-loops and the availability of distal enhancers.
Topics: Humans; Meiosis; Chromosomes; Histones; Gene Expression; Neoplasms
PubMed: 36681477
DOI: 10.1016/bs.ctdb.2022.06.002 -
Current Opinion in Genetics &... Dec 2023Gametogenesis is vulnerable to selfish genetic elements that bias their transmission to the next generation by cheating meiosis. These so-called meiotic drivers are... (Review)
Review
Gametogenesis is vulnerable to selfish genetic elements that bias their transmission to the next generation by cheating meiosis. These so-called meiotic drivers are widespread in plants, animals, and fungi and can impact genome evolution. Here, we summarize recent progress on the causes and consequences of meiotic drive in males, where selfish elements attack vulnerabilities in spermatogenesis. Advances in genomics provide new insights into the organization and dynamics of driving chromosomes in natural populations. Common themes, including small RNAs, gene duplications, and heterochromatin, emerged from these studies. Interdisciplinary approaches combining evolutionary genomics with molecular and cell biology are beginning to unravel the mysteries of drive and suppression mechanisms. These approaches also provide insights into fundamental processes in spermatogenesis and chromatin regulation.
Topics: Animals; Male; Chromosomes; Meiosis
PubMed: 37704518
DOI: 10.1016/j.gde.2023.102111 -
Chromosoma Sep 2019Accurate segregation of homologous chromosomes during meiosis depends on the ability of meiotic cells to promote reciprocal exchanges between parental DNA strands, known... (Review)
Review
Accurate segregation of homologous chromosomes during meiosis depends on the ability of meiotic cells to promote reciprocal exchanges between parental DNA strands, known as crossovers (COs). For most organisms, including budding yeast and other fungi, mammals, nematodes, and plants, the major CO pathway depends on ZMM proteins, a set of molecular actors specifically devoted to recognize and stabilize CO-specific DNA intermediates that are formed during homologous recombination. The progressive implementation of ZMM-dependent COs takes place within the context of the synaptonemal complex (SC), a proteinaceous structure that polymerizes between homologs and participates in close homolog juxtaposition during prophase I of meiosis. While SC polymerization starts from ZMM-bound sites and ZMM proteins are required for SC polymerization in budding yeast and the fungus Sordaria, other organisms differ in their requirement for ZMM in SC elongation. This review provides an overview of ZMM functions and discusses their collaborative tasks for CO formation and SC assembly, based on recent findings and on a comparison of different model organisms.
Topics: Carrier Proteins; Chromosome Pairing; Crossing Over, Genetic; DNA Breaks, Double-Stranded; DNA-Binding Proteins; Homologous Recombination; Meiosis; Phenotype; Protein Binding; Protein Interaction Mapping; Protein Interaction Maps; Protein Multimerization; Saccharomyces cerevisiae
PubMed: 31236671
DOI: 10.1007/s00412-019-00714-8 -
Scientific Reports Sep 2021Dinoflagellates in the family Symbiodiniaceae are obligate endosymbionts of diverse marine invertebrates, including corals, and impact the capacity of their hosts to...
Dinoflagellates in the family Symbiodiniaceae are obligate endosymbionts of diverse marine invertebrates, including corals, and impact the capacity of their hosts to respond to climate change-driven ocean warming. Understanding the conditions under which increased genetic variation in Symbiodiniaceae arises via sexual recombination can support efforts to evolve thermal tolerance in these symbionts and ultimately mitigate coral bleaching, the breakdown of the coral-Symbiodiniaceae partnership under stress. However, direct observations of meiosis in Symbiodiniaceae have not been reported, despite various lines of indirect evidence that it occurs. We present the first cytological evidence of sex in Symbiodiniaceae based on nuclear DNA content and morphology using Image Flow Cytometry, Cell Sorting and Confocal Microscopy. We show the Symbiodiniaceae species, Cladocopium latusorum, undergoes gamete conjugation, zygote formation, and meiosis within a dominant reef-building coral in situ. On average, sex was detected in 1.5% of the cells analyzed (N = 10,000-40,000 cells observed per sample in a total of 20 samples obtained from 3 Pocillopora colonies). We hypothesize that meiosis follows a two-step process described in other dinoflagellates, in which diploid zygotes form dyads during meiosis I, and triads and tetrads as final products of meiosis II. This study sets the stage for investigating environmental triggers of Symbiodiniaceae sexuality and can accelerate the assisted evolution of a key coral symbiont in order to combat reef degradation.
Topics: Coral Reefs; DNA; Dinoflagellida; Flow Cytometry; Meiosis; Microscopy, Confocal; Mitosis; Recombination, Genetic; Reproduction; Zygote
PubMed: 34552138
DOI: 10.1038/s41598-021-98148-9