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Nature Chemical Biology Jul 2018
Topics: Chromosome Pairing; Chromosome Segregation; DNA; DNA Breaks, Double-Stranded; Surgical Instruments
PubMed: 29915230
DOI: 10.1038/s41589-018-0095-3 -
Cell Proliferation Apr 2024The successful progression of meiosis prophase I requires integrating information from the structural and molecular levels. In this study, we show that ZFP541 and KCTD19...
The successful progression of meiosis prophase I requires integrating information from the structural and molecular levels. In this study, we show that ZFP541 and KCTD19 work in the same genetic pathway to regulate the progression of male meiosis and thus fertility. The Zfp541 and/or Kctd19 knockout male mice show various structural and recombination defects including detached chromosome ends, aberrant localization of chromosome axis components and recombination proteins, and globally altered histone modifications. Further analyses on RNA-seq, ChIP-seq, and ATAC-seq data provide molecular evidence for the above defects and reveal that ZFP541/KCTD19 activates the expression of many genes by repressing several major transcription repressors. More importantly, we reveal an unexpected role of ZFP541/KCTD19 in directly modulating chromatin organization. These results suggest that ZFP541/KCTD19 simultaneously regulates the transcription cascade and chromatin organization to ensure the coordinated progression of multiple events at chromosome structural and biochemical levels during meiosis prophase I.
Topics: Animals; Mice; Male; Chromatin; Transcription Factors; Synaptonemal Complex; Protein Processing, Post-Translational; Meiosis; Chromosomal Proteins, Non-Histone
PubMed: 37921559
DOI: 10.1111/cpr.13567 -
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 -
International Journal of Biological... 2022About 10% of reproductive-aged couples suffer from infertility. However, the genetic causes of human infertility cases are largely unknown. Meiosis produces haploid... (Review)
Review
About 10% of reproductive-aged couples suffer from infertility. However, the genetic causes of human infertility cases are largely unknown. Meiosis produces haploid gametes for fertilization and errors in meiosis are associated with human infertility in both males and females. Successful meiosis relies on the assembly of the synaptonemal complex (SC) between paired homologous chromosomes during the meiotic prophase. The SC is ultrastructurally and functionally conserved, promoting inter-homologous recombination and crossover formation, thus critical for accurate meiotic chromosome segregation. With whole-genome/exome sequencing and mouse models, a list of mutations in SC coding genes has been linked to human infertility. Here we summarize those findings. We also analyzed SC gene variants present in the general population and presented complex interaction networks associated with SC components. Whether a combination of genetic variations and environmental factors causes human infertility demands further investigations.
Topics: Adult; Animals; Chromosome Segregation; Female; Germ Cells; Humans; Infertility; Male; Meiosis; Mice; Synaptonemal Complex
PubMed: 35342360
DOI: 10.7150/ijbs.67843 -
Nature Plants Dec 2023The synaptonemal complex (SC) is a proteinaceous structure that forms between homologous chromosomes during meiosis prophase. The SC is widely conserved across species,...
The synaptonemal complex (SC) is a proteinaceous structure that forms between homologous chromosomes during meiosis prophase. The SC is widely conserved across species, but its structure and roles during meiotic recombination are still debated. While the SC central region is made up of transverse filaments and central element proteins in mammals and fungi, few central element proteins have been identified in other species. Here we report the identification of two coiled-coil proteins, SCEP1 and SCEP2, that form a complex and localize at the centre of the Arabidopsis thaliana SC. In scep1 and scep2 mutants, chromosomes are aligned but not synapsed (the ZYP1 transverse filament protein is not loaded), crossovers are increased compared with the wild type, interference is lost and heterochiasmy is strongly reduced. We thus report the identification of two plant SC central elements, and homologues of these are found in all major angiosperm clades.
Topics: Animals; Synaptonemal Complex; Prophase; Arabidopsis; Arabidopsis Proteins; Meiosis; Mammals
PubMed: 37973938
DOI: 10.1038/s41477-023-01558-y -
Cell Cycle (Georgetown, Tex.) 2016
Topics: Animals; Chromosome Pairing; Chromosomes; Humans; Meiosis
PubMed: 26694065
DOI: 10.1080/15384101.2015.1131524 -
Nature Reviews. Genetics Apr 2018Genetic recombination occurs in all organisms and is vital for genome stability. Indeed, in humans, aberrant recombination can lead to diseases such as cancer. Our... (Review)
Review
Genetic recombination occurs in all organisms and is vital for genome stability. Indeed, in humans, aberrant recombination can lead to diseases such as cancer. Our understanding of homologous recombination is built upon more than a century of scientific inquiry, but achieving a more complete picture using ensemble biochemical and genetic approaches is hampered by population heterogeneity and transient recombination intermediates. Recent advances in single-molecule and super-resolution microscopy methods help to overcome these limitations and have led to new and refined insights into recombination mechanisms, including a detailed understanding of DNA helicase function and synaptonemal complex structure. The ability to view cellular processes at single-molecule resolution promises to transform our understanding of recombination and related processes.
Topics: Animals; DNA Helicases; Homologous Recombination; Humans; Neoplasm Proteins; Neoplasms; Synaptonemal Complex
PubMed: 29225334
DOI: 10.1038/nrg.2017.92 -
Science China. Life Sciences Nov 2017Meiosis is a specialized eukaryotic cell division, in which diploid cells undergo a single round of DNA replication and two rounds of nuclear division to produce haploid... (Review)
Review
Meiosis is a specialized eukaryotic cell division, in which diploid cells undergo a single round of DNA replication and two rounds of nuclear division to produce haploid gametes. In most eukaryotes, the core events of meiotic prophase I are chromosomal pairing, synapsis and recombination. To ensure accurate chromosomal segregation, homologs have to identify and align along each other at the onset of meiosis. Although much progress has been made in elucidating meiotic processes, information on the mechanisms underlying chromosome pairing is limited in contrast to the meiotic recombination and synapsis events. Recent research in many organisms indicated that centromere interactions during early meiotic prophase facilitate homologous chromosome pairing, and functional centromere is a prerequisite for centromere pairing such as in maize. Here, we summarize the recent achievements of chromosome pairing research on plants and other organisms, and outline centromere interactions, nuclear chromosome orientation, and meiotic cohesin, as main determinants of chromosome pairing in early meiotic prophase.
Topics: Cell Cycle Proteins; Centromere; Chromosomal Proteins, Non-Histone; Chromosome Pairing; Chromosome Segregation; Homologous Recombination; Kinetics; Meiosis; Meiotic Prophase I; Plants; Telomere; Cohesins
PubMed: 28755295
DOI: 10.1007/s11427-017-9109-y -
DNA Repair Nov 2018Homologous recombination (HR) is a universally conserved mechanism used to maintain genomic integrity. In eukaryotes, HR is used to repair the spontaneous double strand... (Review)
Review
Homologous recombination (HR) is a universally conserved mechanism used to maintain genomic integrity. In eukaryotes, HR is used to repair the spontaneous double strand breaks (DSBs) that arise during mitotic growth, and the programmed DSBs that form during meiosis. The mechanisms that govern mitotic and meiotic HR share many similarities, however, there are also several key differences, which reflect the unique attributes of each process. For instance, even though many of the proteins involved in mitotic and meiotic HR are the same, DNA target specificity is not: mitotic DSBs are repaired primarily using the sister chromatid as a template, whereas meiotic DBSs are repaired primarily through targeting of the homologous chromosome. These changes in template specificity are induced by expression of meiosis-specific HR proteins, down-regulation of mitotic HR proteins, and the formation of meiosis-specific chromosomal structures. Here, we compare and contrast the biochemical properties of key recombination intermediates formed during the pre-synapsis phase of mitotic and meiotic HR. Throughout, we try to highlight unanswered questions that will shape our understanding of how homologous recombination contributes to human cancer biology and sexual reproduction.
Topics: Animals; Chromosome Pairing; Eukaryota; Homologous Recombination; Humans; Meiosis; Mitosis; Rad51 Recombinase
PubMed: 30195641
DOI: 10.1016/j.dnarep.2018.08.018 -
Cell Cycle (Georgetown, Tex.) Aug 2021A central player in meiotic chromosome dynamics is the conserved Polo-like kinase (PLK) family. PLKs are dynamically localized to distinct structures during meiotic... (Review)
Review
A central player in meiotic chromosome dynamics is the conserved Polo-like kinase (PLK) family. PLKs are dynamically localized to distinct structures during meiotic prophase and phosphorylate a diverse group of substrates to control homolog pairing, synapsis, and meiotic recombination. In a recent study, we uncovered the mechanisms that control the targeting of a meiosis-specific PLK-2 in . In early meiotic prophase, PLK-2 localizes to special chromosome regions known as pairing centers and drives homolog pairing and synapsis. PLK-2 then relocates to the synaptonemal complex (SC) after crossover designation and mediates chromosome remodeling required for homolog separation. What controls this intricate targeting of PLK-2 in space and time? We discuss recent findings and remaining questions for the future.
Topics: Animals; Binding Sites; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Chromosome Pairing; Chromosomes; Gene Expression Regulation; Meiosis; Meiotic Prophase I; Phosphorylation; Protein Binding; Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 34266376
DOI: 10.1080/15384101.2021.1953232