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BioEssays : News and Reviews in... Nov 2001Meiosis is the process by which diploid germ cells divide to produce haploid gametes for sexual reproduction. The process is highly conserved in eukaryotes, however the... (Review)
Review
Meiosis is the process by which diploid germ cells divide to produce haploid gametes for sexual reproduction. The process is highly conserved in eukaryotes, however the recent availability of mouse models for meiotic recombination has revealed surprising regulatory differences between simple unicellular organisms and those with increasingly complex genomes. Moreover, in these higher eukaryotes, the intervention of physiological and sex-specific factors may also influence how meiotic recombination and progression are monitored and regulated. This review will focus on the recent studies involving mouse mutants for meiosis, and will highlight important differences between traditional model systems for meiosis (such as yeast) and those involving more complex cellular, physiological and genetic criteria.
Topics: Animals; Humans; Mammals; Meiosis; Mice; Prophase; Recombination, Genetic
PubMed: 11746216
DOI: 10.1002/bies.1145 -
Current Biology : CB Mar 2021Cathleen Lake and Scott Hawley discuss the components, assembly and functional importance of the synaptonemal complex.
Cathleen Lake and Scott Hawley discuss the components, assembly and functional importance of the synaptonemal complex.
Topics: Animals; Chromosome Pairing; Chromosome Segregation; Crossing Over, Genetic; Humans; Meiosis; Schizosaccharomyces; Synaptonemal Complex
PubMed: 33689714
DOI: 10.1016/j.cub.2021.01.015 -
Developmental Cell Dec 2023During meiosis, the chromatin and transcriptome undergo prominent switches. Although recent studies have explored the genome reorganization during spermatogenesis, the...
During meiosis, the chromatin and transcriptome undergo prominent switches. Although recent studies have explored the genome reorganization during spermatogenesis, the chromatin remodeling in oogenesis and characteristics of homologous pairing remain largely elusive. We comprehensively compared chromatin structures and transcriptomes at successive substages of meiotic prophase in both female and male mice using low-input high-through chromosome conformation capture (Hi-C) and RNA sequencing (RNA-seq). Compartments and topologically associating domains (TADs) gradually disappeared and slowly recovered in both sexes. We found that homologs adopted different sex-conserved pairing strategies prior to and after the leptotene-to-zygotene transition, changing from long interspersed nuclear element (LINE)-enriched compartments B to short interspersed nuclear element (SINE)-enriched compartments A. We complemented marker genes and predicted the sex-specific meiotic sterile genes for each substage. This study provides valuable insights into the similarities and distinctions between sexes in chromosome architecture, homologous pairing, and transcriptome during meiotic prophase of both oogenesis and spermatogenesis.
Topics: Male; Female; Mice; Animals; Meiosis; Spermatogenesis; Prophase; Meiotic Prophase I; Chromatin; Oogenesis; Chromosome Pairing
PubMed: 37963468
DOI: 10.1016/j.devcel.2023.10.009 -
Annual Review of Physiology 2012We review the critical events in early meiotic prophase in Drosophila melanogaster oocytes. We focus on four aspects of this process: the formation of the synaptonemal... (Review)
Review
We review the critical events in early meiotic prophase in Drosophila melanogaster oocytes. We focus on four aspects of this process: the formation of the synaptonemal complex (SC) and its role in maintaining homologous chromosome pairings, the critical roles of the meiosis-specific process of centromere clustering in the formation of a full-length SC, the mechanisms by which preprogrammed double-strand breaks initiate meiotic recombination, and the checkpoints that govern the progression and coordination of these processes. Central to this discussion are the roles that somatic pairing events play in establishing the necessary conditions for proper SC formation, the roles of centromere pairing in synapsis initiation, and the mechanisms by which oocytes detect failures in SC formation and/or recombination. Finally, we correlate what is known in Drosophila oocytes with our understanding of these processes in other systems.
Topics: Animals; Cell Nucleus; Centromere; Chromosome Pairing; Chromosomes; DNA Breaks, Double-Stranded; DNA Damage; Drosophila; Female; Humans; Meiosis; Meiotic Prophase I; Oocytes; Pachytene Stage; Synaptonemal Complex; Telomere
PubMed: 22335798
DOI: 10.1146/annurev-physiol-020911-153342 -
Proceedings of the National Academy of... Mar 2022SignificanceEssential for sexual reproduction, meiosis is a specialized cell division required for the production of haploid gametes. Critical to this process are the...
SignificanceEssential for sexual reproduction, meiosis is a specialized cell division required for the production of haploid gametes. Critical to this process are the pairing, recombination, and segregation of homologous chromosomes (homologs). While pairing and recombination are linked, it is not known how many linkages are sufficient to hold homologs in proximity. Here, we reveal that random diffusion and the placement of a small number of linkages are sufficient to establish the apparent "pairing" of homologs. We also show that colocalization between any two loci is more dynamic than anticipated. Our study provides observations of live interchromosomal dynamics during meiosis and illustrates the power of combining single-cell measurements with theoretical polymer modeling.
Topics: Chromosomes; Meiosis; Prophase
PubMed: 35302885
DOI: 10.1073/pnas.2115883119 -
Development (Cambridge, England) Apr 2018To prevent chromosomal aberrations being transmitted to the offspring, strict meiotic checkpoints are in place to remove aberrant spermatocytes. However, in about 1% of...
To prevent chromosomal aberrations being transmitted to the offspring, strict meiotic checkpoints are in place to remove aberrant spermatocytes. However, in about 1% of males these checkpoints cause complete meiotic arrest leading to azoospermia and subsequent infertility. Here, we unravel two clearly distinct meiotic arrest mechanisms that occur during prophase of human male meiosis. Type I arrested spermatocytes display severe asynapsis of the homologous chromosomes, disturbed XY-body formation and increased expression of the Y chromosome-encoded gene and seem to activate a DNA damage pathway leading to induction of p63, possibly causing spermatocyte apoptosis. Type II arrested spermatocytes display normal chromosome synapsis, normal XY-body morphology and meiotic crossover formation but have a lowered expression of several cell cycle regulating genes and fail to silence the X chromosome-encoded gene Discovery and understanding of these meiotic arrest mechanisms increases our knowledge of how genomic stability is guarded during human germ cell development.
Topics: Apoptosis; Azoospermia; Cell Cycle Checkpoints; DNA Damage; DNA Repair; Gene Expression Profiling; Humans; Kruppel-Like Transcription Factors; Male; Meiosis; Prophase; Spermatocytes; Spermatogenesis; Transcription Factors; Tumor Suppressor Proteins
PubMed: 29540502
DOI: 10.1242/dev.160614 -
PLoS Genetics Mar 2024During meiosis, genetic recombination is initiated by the formation of many DNA double-strand breaks (DSBs) catalysed by the evolutionarily conserved topoisomerase-like...
During meiosis, genetic recombination is initiated by the formation of many DNA double-strand breaks (DSBs) catalysed by the evolutionarily conserved topoisomerase-like enzyme, Spo11, in preferred genomic sites known as hotspots. DSB formation activates the Tel1/ATM DNA damage responsive (DDR) kinase, locally inhibiting Spo11 activity in adjacent hotspots via a process known as DSB interference. Intriguingly, in S. cerevisiae, over short genomic distances (<15 kb), Spo11 activity displays characteristics of concerted activity or clustering, wherein the frequency of DSB formation in adjacent hotspots is greater than expected by chance. We have proposed that clustering is caused by a limited number of sub-chromosomal domains becoming primed for DSB formation. Here, we provide evidence that DSB clustering is abolished when meiotic prophase timing is extended via deletion of the NDT80 transcription factor. We propose that extension of meiotic prophase enables most cells, and therefore most chromosomal domains within them, to reach an equilibrium state of similar Spo11-DSB potential, reducing the impact that priming has on estimates of coincident DSB formation. Consistent with this view, when Tel1 is absent but Ndt80 is present and thus cells are able to rapidly exit meiotic prophase, genome-wide maps of Spo11-DSB formation are skewed towards pericentromeric regions and regions that load pro-DSB factors early-revealing regions of preferential priming-but this effect is abolished when NDT80 is deleted. Our work highlights how the stochastic nature of Spo11-DSB formation in individual cells within the limited temporal window of meiotic prophase can cause localised DSB clustering-a phenomenon that is exacerbated in tel1Δ cells due to the dual roles that Tel1 has in DSB interference and meiotic prophase checkpoint control.
Topics: DNA; DNA Breaks, Double-Stranded; DNA-Binding Proteins; Endodeoxyribonucleases; Intracellular Signaling Peptides and Proteins; Meiosis; Prophase; Protein Serine-Threonine Kinases; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 38427688
DOI: 10.1371/journal.pgen.1011140 -
Cytogenetic and Genome Research 2003During the male meiotic prophase in mouse and man, pairing and recombination of homologous chromosomes is accompanied by changes in chromatin structure. In this review,... (Review)
Review
During the male meiotic prophase in mouse and man, pairing and recombination of homologous chromosomes is accompanied by changes in chromatin structure. In this review, the dynamics of assembly and disassembly of the chromatin-associated complexes that mediate sister chromatid cohesion (cohesin) and maintain chromosome pairing (the synaptonemal complex) are described. Special features of the meiotic S phase are discussed, and also the dynamics of several key players that act together after the S phase at sites of meiotic double-strand break DNA repair. Current knowledge on histone modifications that occur during the male meiotic prophase is discussed, with special attention for the inactive chromatin of the X and Y chromosomes that constitutes the sex body. Finally, it is discussed that in the future, it will be possible to view the true chromatin dynamics during male meiosis in time, in living cells, through analysis of fluorescent-tagged proteins expressed in transgenic mice, using advanced fluorescent microscopy techniques.
Topics: Animals; Chromatin; DNA Repair; DNA Replication; Histones; Male; Meiosis; Mice; Prophase; Recombination, Genetic; Sex Chromosomes; Spermatozoa; Synaptonemal Complex
PubMed: 15051943
DOI: 10.1159/000076808 -
Methods in Molecular Biology (Clifton,... 2009Most of the human aneuploidies have a maternal origin. This feature makes the study of human female meiosis a fundamental topic to understand the reasons leading to this... (Review)
Review
Most of the human aneuploidies have a maternal origin. This feature makes the study of human female meiosis a fundamental topic to understand the reasons leading to this important social problem. Unfortunately, due to sample collection difficulties, not many studies have been performed on human female meiotic prophase. In this chapter we present a comprehensive collection of protocols that allows the study of human female meiotic prophase through different technical approaches using both spread and structurally preserved oocytes.
Topics: Cytogenetic Analysis; Cytological Techniques; Female; Humans; Meiosis; Ovary; Prophase
PubMed: 19685338
DOI: 10.1007/978-1-60761-103-5_24 -
Cells Jun 2023The synaptonemal complex (SC) is a meiosis-specific multiprotein complex that forms between homologous chromosomes during prophase of meiosis I. Upon assembly, the SC... (Review)
Review
The synaptonemal complex (SC) is a meiosis-specific multiprotein complex that forms between homologous chromosomes during prophase of meiosis I. Upon assembly, the SC mediates the synapses of the homologous chromosomes, leading to the formation of bivalents, and physically supports the formation of programmed double-strand breaks (DSBs) and their subsequent repair and maturation into crossovers (COs), which are essential for genome haploidization. Defects in the assembly of the SC or in the function of the associated meiotic recombination machinery can lead to meiotic arrest and human infertility. The majority of proteins and complexes involved in these processes are exclusively expressed during meiosis or harbor meiosis-specific subunits, although some have dual functions in somatic DNA repair and meiosis. Consistent with their functions, aberrant expression and malfunctioning of these genes have been associated with cancer development. In this review, we focus on the significance of the SC and their meiotic-associated proteins in human fertility, as well as how human genetic variants encoding for these proteins affect the meiotic process and contribute to infertility and cancer development.
Topics: Synaptonemal Complex; Humans; Meiosis; Neoplasms; Infertility; Male; Female; Recombination, Genetic
PubMed: 37443752
DOI: 10.3390/cells12131718