scholarly journals Spatial Regulation of Polo-like Kinase Activity during C. elegans Meiosis by the Nucleoplasmic HAL-2/HAL-3 Complex

2019 ◽  
Author(s):  
Baptiste Roelens ◽  
Consuelo Barroso ◽  
Alex Montoya ◽  
Pedro Cutillas ◽  
Weibin Zhang ◽  
...  
Keyword(s):  
Protein Complex ◽  
Homologous Chromosomes ◽  
C Elegans ◽  
Spatial Regulation ◽  
Homolog Pairing ◽  
Cellular Events ◽  
Important Player ◽  
Correct Pairing ◽  
Unpaired Chromosome ◽  
Key Events

AbstractProper partitioning of homologous chromosomes during meiosis relies on the coordinated execution of multiple interconnected events: Homologs must locate, recognize and align with their correct pairing partners. Further, homolog pairing must be coupled to assembly of the synaptonemal complex (SC), a meiosis-specific tripartite structure that maintains stable associations between the axes of aligned homologs and regulates formation of crossovers between their DNA molecules to create linkages that enable their segregation. Here we identify HAL-3 (Homolog Alignment 3) as an important player in coordinating these key events during C. elegans meiosis. HAL-3 and the previously-identified HAL-2 are interacting and interdependent components of a protein complex that localizes to the nucleoplasm of germ cells. hal-3 (or hal-2) mutants exhibit multiple meiotic prophase defects including failure to establish homolog pairing, inappropriate loading of SC subunits onto unpaired chromosome axes, and premature loss of synapsis checkpoint protein PCH-2. Further, loss of hal function results in misregulation of the subcellular localization and activity of polo-like kinases (PLK-1 and PLK-2), which dynamically localize to different defined subnuclear sites during wild-type prophase progression to regulate distinct cellular events. Moreover, loss of PLK-2 activity partially restores tripartite SC structure in a hal mutant background, suggesting that the defect in pairwise SC assembly in hal mutants reflects inappropriate PLK activity. Together our data support a model in which the nucleoplasmic HAL-2/HAL-3 protein complex constrains both localization and activity of meiotic Polo-like kinases, thereby preventing premature interaction with stage-inappropriate targets.

scholarly journals The Zebrafish Meiotic Cohesin Complex Protein Smc1b Is Required for Key Events in Meiotic Prophase I

2021 ◽  
Vol 9 ◽  
Author(s):  
Kazi Nazrul Islam ◽  
Maitri Mitesh Modi ◽  
Kellee Renee Siegfried
Keyword(s):  
Essential Role ◽  
Cohesin Complex ◽  
Dna Double Strand Breaks ◽  
Homologous Chromosomes ◽  
Homolog Pairing ◽  
Complex Protein ◽  
Complete Failure ◽  
Cell Arrest ◽  
Key Events

The eukaryotic structural maintenance of chromosomes (SMC) proteins are involved in key processes of chromosome structure and dynamics. SMC1β was identified as a component of the meiotic cohesin complex in vertebrates, which aids in keeping sister chromatids together prior to segregation in meiosis II and is involved in association of homologous chromosomes in meiosis I. The role of SMC1β in meiosis has primarily been studied in mice, where mutant male and female mice are infertile due to germ cell arrest at pachytene and metaphase II stages, respectively. Here, we investigate the function of zebrafish Smc1b to understand the role of this protein more broadly in vertebrates. We found that zebrafish smc1b is necessary for fertility and has important roles in meiosis, yet has no other apparent roles in development. Therefore, smc1b functions primarily in meiosis in both fish and mammals. In zebrafish, we showed that smc1b mutant spermatocytes initiated telomere clustering in leptotene, but failed to complete this process and progress into zygotene. Furthermore, mutant spermatocytes displayed a complete failure of synapsis between homologous chromosomes and homolog pairing only occurred at chromosome ends. Interestingly, meiotic DNA double strand breaks occurred in the absence of Smc1b despite failed pairing and synapsis. Overall, our findings point to an essential role of Smc1b in the leptotene to zygotene transition during zebrafish spermatogenesis. In addition, ovarian follicles failed to form in smc1b mutants, suggesting an essential role in female meiosis as well. Our results indicate that there are some key differences in Smc1b requirement in meiosis among vertebrates: while Smc1b is not required for homolog pairing and synapsis in mice, it is essential for these processes in zebrafish.

scholarly journals Synaptonemal complex components are required for meiotic checkpoint function in C. elegans

2016 ◽  
Author(s):  
Tisha Bohr ◽  
Guinevere Ashley ◽  
Evan Eggleston ◽  
Kyra Firestone ◽  
Needhi Bhalla
Keyword(s):  
Synaptonemal Complex ◽  
Chromosome Segregation ◽  
Meiotic Chromosome ◽  
Checkpoint Response ◽  
Homologous Chromosomes ◽  
C Elegans ◽  
Homolog Pairing ◽  
The Stability ◽  
Complex Components

AbstractSynapsis involves the assembly of a proteinaceous structure, the synaptonemal complex (SC), between paired homologous chromosomes and is essential for proper meiotic chromosome segregation. In C. elegans, the synapsis checkpoint selectively removes nuclei with unsynapsed chromosomes by inducing apoptosis. This checkpoint depends on Pairing Centers (PCs), cis-acting sites that promote pairing and synapsis. We have hypothesized that the stability of homolog pairing at PCs is monitored by this checkpoint. Here, we report that SC components SYP-3, HTP-3, HIM-3 and HTP-1 are required for a functional synapsis checkpoint. Mutation of these components does not abolish PC function, demonstrating they are bonafide checkpoint components. Further, we identify mutant backgrounds in which the instability of homolog pairing at PCs does not correlate with the synapsis checkpoint response. Altogether, these data suggest that, in addition to homolog pairing, SC assembly may be monitored by the synapsis checkpoint.

scholarly journals Atypical Protein Kinase C Is Involved in the Evolutionarily Conserved Par Protein Complex and Plays a Critical Role in Establishing Epithelia-Specific Junctional Structures

2001 ◽  
Vol 152 (6) ◽  
pp. 1183-1196 ◽  
Author(s):  
Atsushi Suzuki ◽  
Tomoyuki Yamanaka ◽  
Tomonori Hirose ◽  
Naoyuki Manabe ◽  
Keiko Mizuno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Polarity ◽  
Protein Complex ◽  
Mdck Cells ◽  
Critical Role ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Surface Polarity ◽  
C Elegans ◽  
Evolutionarily Conserved

We have previously shown that during early Caenorhabditis elegans embryogenesis PKC-3, a C. elegans atypical PKC (aPKC), plays critical roles in the establishment of cell polarity required for subsequent asymmetric cleavage by interacting with PAR-3 [Tabuse, Y., Y. Izumi, F. Piano, K.J. Kemphues, J. Miwa, and S. Ohno. 1998. Development (Camb.). 125:3607–3614]. Together with the fact that aPKC and a mammalian PAR-3 homologue, aPKC-specific interacting protein (ASIP), colocalize at the tight junctions of polarized epithelial cells (Izumi, Y., H. Hirose, Y. Tamai, S.-I. Hirai, Y. Nagashima, T. Fujimoto, Y. Tabuse, K.J. Kemphues, and S. Ohno. 1998. J. Cell Biol. 143:95–106), this suggests a ubiquitous role for aPKC in establishing cell polarity in multicellular organisms. Here, we show that the overexpression of a dominant-negative mutant of aPKC (aPKCkn) in MDCK II cells causes mislocalization of ASIP/PAR-3. Immunocytochemical analyses, as well as measurements of paracellular diffusion of ions or nonionic solutes, demonstrate that the biogenesis of the tight junction structure itself is severely affected in aPKCkn-expressing cells. Furthermore, these cells show increased interdomain diffusion of fluorescent lipid and disruption of the polarized distribution of Na+,K+-ATPase, suggesting that epithelial cell surface polarity is severely impaired in these cells. On the other hand, we also found that aPKC associates not only with ASIP/PAR-3, but also with a mammalian homologue of C. elegans PAR-6 (mPAR-6), and thereby mediates the formation of an aPKC-ASIP/PAR-3–PAR-6 ternary complex that localizes to the apical junctional region of MDCK cells. These results indicate that aPKC is involved in the evolutionarily conserved PAR protein complex, and plays critical roles in the development of the junctional structures and apico-basal polarization of mammalian epithelial cells.

scholarly journals Synaptonemal Complex dimerization regulates chromosome alignment and crossover patterning in meiosis

2020 ◽  
Author(s):  
Spencer G. Gordon ◽  
Lisa E. Kursel ◽  
Kewei Xu ◽  
Ofer Rog
Keyword(s):  
Synaptonemal Complex ◽  
Sequence Homology ◽  
Genetic Information ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Homologous Chromosomes ◽  
C Elegans ◽  
Local Sequence ◽  
Chromosome Alignment ◽  
Dimerization Interface

AbstractDuring sexual reproduction the parental homologous chromosomes find each other (pair) and align along their lengths by integrating local sequence homology with large-scale contiguity, thereby allowing for precise exchange of genetic information. The Synaptonemal Complex (SC) is a conserved zipper-like structure that assembles between the homologous chromosomes. This phase-separated interface brings chromosomes together and regulates exchanges between them. However, the molecular mechanisms by which the SC carries out these functions remain poorly understood. Here we isolated and characterized two mutations in the dimerization interface in the middle of the SC zipper in C. elegans. The mutations perturb both chromosome alignment and the regulation of genetic exchanges. Underlying the chromosome-scale phenotypes are distinct alterations to the way SC subunits interact with one another. We propose that the SC brings homologous chromosomes together through two biophysical activities: obligate dimerization that prevents assembly on unpaired chromosomes; and a tendency to phase-separate that extends pairing interactions along the entire length of the chromosomes.

scholarly journals Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in Drosophila

2020 ◽  
Author(s):  
Myron Child ◽  
Jack R. Bateman ◽  
Amir Jahangiri ◽  
Armando Reimer ◽  
Nicholas C. Lammers ◽  
...  
Keyword(s):  
Spatial Configuration ◽  
Live Imaging ◽  
Biophysical Model ◽  
Structural Basis ◽  
Biophysical Modeling ◽  
Homologous Chromosomes ◽  
3D Genome ◽  
Homolog Pairing ◽  
Rna Labeling ◽  
Regulated Gene Expression

AbstractThe spatial configuration of the eukaryotic genome is organized and dynamic, providing the structural basis for regulated gene expression in living cells. In Drosophila melanogaster, 3D genome organization is characterized by somatic homolog pairing, where homologous chromosomes are intimately paired from end to end; however, the process by which homologs identify one another and pair has remained mysterious. A recent model proposed that specifically interacting “buttons” encoded along the lengths of homologous chromosomes drive somatic homolog pairing. Here, we turned this hypothesis into a precise biophysical model to demonstrate that a button-based mechanism can lead to chromosome-wide pairing. We tested our model and constrained its free parameters using live-imaging measurements of chromosomal loci tagged with the MS2 and PP7 nascent RNA labeling systems. Our analysis showed strong agreement between model predictions and experiments in the separation dynamics of tagged homologous loci as they transition from unpaired to paired states, and in the percentage of nuclei that become paired as embryonic development proceeds. In sum, as a result of this dialogue between theory and experiment, our data strongly support a button-based mechanism of somatic homolog pairing in Drosophila and provide a theoretical framework for revealing the molecular identity and regulation of buttons.

SDC-3 coordinates the assembly of a dosage compensation complex on the nematode X chromosome

Development ◽  
1997 ◽  
Vol 124 (5) ◽  
pp. 1019-1031 ◽  
Author(s):  
T.L. Davis ◽  
B.J. Meyer
Keyword(s):  
Zinc Finger ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Protein Complex ◽  
Terminal Region ◽  
X Chromosomes ◽  
C Elegans ◽  
Amino Terminal ◽  
Zinc Finger Motifs ◽  
Specific Association

X chromosome expression in C. elegans is controlled by a chromosome-wide regulatory process called dosage compensation that specifically reduces by half the level of transcripts made from each hermaphrodite X chromosome. This process equalizes X expression between the sexes (XX hermaphrodites and XO males), despite their two-fold difference in X chromosome dose, and thereby prevents sex-specific lethality. Dosage compensation is achieved by a protein complex that associates with X in a sex-specific fashion to modulate gene expression. SDC-3, a protein that coordinately controls both sex determination and dosage compensation, activates dosage compensation by directing the dosage compensation protein complex to the hermaphrodite X chromosomes. We show that SDC-3 coordinates this assembly through its own sex-specific association with X. SDC-3 in turn requires other members of the dosage compensation gene hierarchy for its stability and its X localization. In addition, SDC-3 requires its own zinc finger motifs and an amino-terminal region for its X association. Our experiments suggest the possible involvement of zinc finger motifs in X chromosome recognition and the amino-terminal region in interactions with other dosage compensation proteins.

scholarly journals Regulation of the meiotic divisions of mammalian oocytes and eggs

2018 ◽  
Vol 46 (4) ◽  
pp. 797-806 ◽  
Author(s):  
Jessica R. Sanders ◽  
Keith T. Jones
Keyword(s):  
Cell Division ◽  
Luteinizing Hormone ◽  
Spindle Assembly Checkpoint ◽  
Asymmetric Cell Division ◽  
Homologous Chromosomes ◽  
Mammalian Oocyte ◽  
Cellular Events ◽  
The Hours ◽  
Meiosis I

Initiated by luteinizing hormone and finalized by the fertilizing sperm, the mammalian oocyte completes its two meiotic divisions. The first division occurs in the mature Graafian follicle during the hours preceding ovulation and culminates in an extreme asymmetric cell division and the segregation of the two pairs of homologous chromosomes. The newly created mature egg rearrests at metaphase of the second meiotic division prior to ovulation and only completes meiosis following a Ca2+ signal initiated by the sperm at gamete fusion. Here, we review the cellular events that govern the passage of the oocyte through meiosis I with a focus on the role of the spindle assembly checkpoint in regulating its timing. In meiosis II, we examine how the egg achieves its arrest and how the fertilization Ca2+ signal allows the initiation of embryo development.

scholarly journals Mixing and Matching Chromosomes during Female Meiosis

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 696
Author(s):  
Thomas Rubin ◽  
Nicolas Macaisne ◽  
Jean-René Huynh
Keyword(s):  
Female Meiosis ◽  
Homologous Chromosomes ◽  
C Elegans ◽  
Similarities And Differences ◽  
Segregation Of Chromosomes

Meiosis is a key event in the manufacturing of an oocyte. During this process, the oocyte creates a set of unique chromosomes by recombining paternal and maternal copies of homologous chromosomes, and by eliminating one set of chromosomes to become haploid. While meiosis is conserved among sexually reproducing eukaryotes, there is a bewildering diversity of strategies among species, and sometimes within sexes of the same species, to achieve proper segregation of chromosomes. Here, we review the very first steps of meiosis in females, when the maternal and paternal copies of each homologous chromosomes have to move, find each other and pair. We explore the similarities and differences observed in C. elegans, Drosophila, zebrafish and mouse females.

scholarly journals akirin is required for diakinesis bivalent structure and synaptonemal complex disassembly at meiotic prophase I

2013 ◽  
Vol 24 (7) ◽  
pp. 1053-1067 ◽  
Author(s):  
Amy M. Clemons ◽  
Heather M. Brockway ◽  
Yizhi Yin ◽  
Bhavatharini Kasinathan ◽  
Yaron S. Butterfield ◽  
...  
Keyword(s):  
Synaptonemal Complex ◽  
Meiotic Prophase ◽  
Chromosome Condensation ◽  
Late Prophase ◽  
Homologous Chromosomes ◽  
Prophase I ◽  
Meiotic Prophase I ◽  
Evolutionarily Conserved ◽  
Key Events

During meiosis, evolutionarily conserved mechanisms regulate chromosome remodeling, leading to the formation of a tight bivalent structure. This bivalent, a linked pair of homologous chromosomes, is essential for proper chromosome segregation in meiosis. The formation of a tight bivalent involves chromosome condensation and restructuring around the crossover. The synaptonemal complex (SC), which mediates homologous chromosome association before crossover formation, disassembles concurrently with increased condensation during bivalent remodeling. Both chromosome condensation and SC disassembly are likely critical steps in acquiring functional bivalent structure. The mechanisms controlling SC disassembly, however, remain unclear. Here we identify akir-1 as a gene involved in key events of meiotic prophase I in Caenorhabditis elegans. AKIR-1 is a protein conserved among metazoans that lacks any previously known function in meiosis. We show that akir-1 mutants exhibit severe meiotic defects in late prophase I, including improper disassembly of the SC and aberrant chromosome condensation, independently of the condensin complexes. These late-prophase defects then lead to aberrant reconfiguring of the bivalent. The meiotic divisions are delayed in akir-1 mutants and are accompanied by lagging chromosomes. Our analysis therefore provides evidence for an important role of proper SC disassembly in configuring a functional bivalent structure.

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