scholarly journals Mammalian Protein SCP1 Forms Synaptonemal Complex-like Structures in the Absence of Meiotic Chromosomes

2005 ◽  
Vol 16 (1) ◽  
pp. 212-217 ◽  
Author(s):  
Rupert Öllinger ◽  
Manfred Alsheimer ◽  
Ricardo Benavente
Keyword(s):  
Chromosome Segregation ◽  
Meiotic Prophase ◽  
Experimental Conditions ◽  
Homologous Chromosomes ◽  
Meiotic Chromosomes ◽  
Heterologous System ◽  
Primary Determinant ◽  
Specific Proteins ◽  
Mammalian Protein

Synaptonemal complexes (SCs) are evolutionary conserved, meiosis-specific structures that play a central role in synapsis of homologous chromosomes, chiasmata distribution, and chromosome segregation. However, it is still for the most part unclear how SCs do assemble during meiotic prophase. Major components of mammalian SCs are the meiosis-specific proteins SCP1, 2, and 3. To investigate the role of SCP1 in SC assembly, we expressed SCP1 in a heterologous system, i.e., in COS-7 cells that normally do not express SC proteins. Notably, under these experimental conditions SCP1 is able to form structures that closely resemble SCs (i.e., polycomplexes). Moreover, we show that mutations that modify the length of the central α-helical domain of SCP1 influence the width of polycomplexes. Finally, we demonstrate that deletions of the nonhelical N- or C-termini both affect polycomplex assembly, although in a different manner. We conclude that SCP1 is a primary determinant of SC assembly that plays a key role in synapsis of homologous chromosomes.

scholarly journals Shugoshin protects centromere pairing and promotes segregation of non-exchange partner chromosomes in meiosis

2018 ◽  
Author(s):  
Luciana Previato de Almeida ◽  
Jared M. Evatt ◽  
Hoa H. Chuong ◽  
Emily L. Kurdzo ◽  
Craig A. Eyster ◽  
...  
Keyword(s):  
Synaptonemal Complex ◽  
Chromosome Segregation ◽  
Meiotic Prophase ◽  
Single Unit ◽  
Meiotic Chromosome ◽  
Model Systems ◽  
Meiotic Spindle ◽  
Homologous Chromosomes ◽  
Meiosis I

ABSTRACTFaithful chromosome segregation during meiosis I depends upon the formation of connections between homologous chromosomes. Crossovers between homologs connect the partners allowing them to attach to the meiotic spindle as a unit, such that they migrate away from one another at anaphase I. Homologous partners also become connected by pairing of their centromeres in meiotic prophase. This centromere pairing can promote proper segregation at anaphase I of partners that have failed to become joined by a crossover. Centromere pairing is mediated by synaptonemal complex (SC) proteins that persist at the centromere when the SC disassembles. Here, using mouse spermatocyte and yeast model systems, we tested the role of shugoshin in promoting meiotic centromere pairing by protecting centromeric synaptonemal components from disassembly. The results show that shugoshin protects centromeric SC in meiotic prophase and, in anaphase, promotes the proper segregation of partner chromosomes that are not linked by a crossover.SIGNIFICANCEMeiotic crossovers form a connection between homologous chromosomes that allows them to attach to the spindle as a single unit in meiosis I. In humans, failures in this process are a leading cause of aneuploidy. A recently described process, called centromere pairing, can also help connect meiotic chromosome partners in meiosis. Homologous chromosomes become tightly joined by a structure called the synaptonemal complex (SC) in meiotic prophase. After the SC disassembles, persisting SC proteins at the centromeres mediate their pairing. Here, studies in mouse spermatocytes and yeast are used to show that the shugoshin protein helps SC components persist at centromeres and helps centromere pairing promote the proper segregation of yeast chromosomes that fail to become tethered by crossovers.

scholarly journals Meiosis-specific prophase-like pathway controls cleavage-independent release of cohesin by Wapl phosphorylation

2018 ◽  
Author(s):  
Kiran Challa ◽  
V Ghanim Fajish ◽  
Miki Shinohara ◽  
Franz Klein ◽  
Susan M. Gasser ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Meiotic Prophase ◽  
Budding Yeast ◽  
Cell Cycle Regulators ◽  
Late Prophase ◽  
Homologous Chromosomes ◽  
Prophase I ◽  
Meiotic Prophase I ◽  
Meiotic Chromosomes

AbstractSister chromatid cohesion on chromosome arms is essential for the segregation of homologous chromosomes during meiosis I while it is dispensable for sister chromatid separation during mitosis. It was assumed that, unlike the situation in mitosis, chromosome arms retain cohesion prior to onset of anaphase-I. Paradoxically, reduced immunostaining signals of meiosis-specific cohesin, including the kleisin Rec8, from the chromosomes were observed during late prophase-I of budding yeast. This decrease is seen in the absence of Rec8 cleavage and depends on condensin-mediated recruitment of Polo-like kinase (PLK/Cdc5). In this study, we confirmed that this release indeed accompanies the dissociation of acetylated Smc3 as well as Rec8 from meiotic chromosomes during late prophase-I. This release requires, in addition to PLK, the cohesin regulator, Wapl (Rad61/Wpl1 in yeast), and Dbf4-dependent Cdc7 kinase (DDK). Meiosis-specific phosphorylation of Rad61/Wpl1 and Rec8 by PLK and DDK collaboratively promote this release. This process is similar to the vertebrate “prophase” pathway for cohesin release during G2 phase and pro-metaphase. In yeast, meiotic cohesin release coincides with PLK-dependent compaction of chromosomes in late meiotic prophase-I. We suggest that yeast uses this highly regulated cleavage-independent pathway to remove cohesin during late prophase-I to facilitate morphogenesis of condensed metaphase-I chromosomes.Author SummaryIn meiosis the life and health of future generations is decided upon. Any failure in chromosome segregation has a detrimental impact. Therefore, it is currently believed that the physical connections between homologous chromosomes are maintained by meiotic cohesin with exceptional stability. Indeed, it was shown that cohesive cohesin does not show an appreciable turnover during long periods in oocyte development. In this context, it was long assumed but not properly investigated, that the prophase pathway for cohesin release would be specific to mitotic cells and will be safely suppressed during meiosis so as not to endanger the valuable chromosome connections. However, a previous study on budding yeast meiosis suggests the presence of cleavage-independent pathway of cohesin release during late prophase-I. In the work presented here we confirmed that the prophase pathway is not suppressed during meiosis, at least in budding yeast and showed that this cleavage-independent release is regulated by meiosis-specific phosphorylation of two cohesin subunits, Rec8 and Rad61(Wapl) by two cell-cycle regulators, PLK and DDK. Our results suggest that late meiotic prophase-I actively controls cohesin dynamics on meiotic chromosomes for chromosome segregation.

scholarly journals Shugoshin protects centromere pairing and promotes segregation of nonexchange partner chromosomes in meiosis

2019 ◽  
Vol 116 (19) ◽  
pp. 9417-9422 ◽  
Author(s):  
Luciana Previato de Almeida ◽  
Jared M. Evatt ◽  
Hoa H. Chuong ◽  
Emily L. Kurdzo ◽  
Craig A. Eyster ◽  
...  
Keyword(s):  
Synaptonemal Complex ◽  
Chromosome Segregation ◽  
Meiotic Prophase ◽  
Model Systems ◽  
Meiotic Spindle ◽  
Homologous Chromosomes ◽  
Meiosis I ◽  
Yeast Model

Faithful chromosome segregation during meiosis I depends upon the formation of connections between homologous chromosomes. Crossovers between homologs connect the partners, allowing them to attach to the meiotic spindle as a unit, such that they migrate away from one another at anaphase I. Homologous partners also become connected by pairing of their centromeres in meiotic prophase. This centromere pairing can promote proper segregation at anaphase I of partners that have failed to become joined by a crossover. Centromere pairing is mediated by synaptonemal complex (SC) proteins that persist at the centromere when the SC disassembles. Here, using mouse spermatocyte and yeast model systems, we tested the role of shugoshin in promoting meiotic centromere pairing by protecting centromeric synaptonemal components from disassembly. The results show that shugoshin protects the centromeric SC in meiotic prophase and, in anaphase, promotes the proper segregation of partner chromosomes that are not linked by a crossover.

scholarly journals A molecular model for the role of SYCP3 in meiotic chromosome organisation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Johanna Liinamaria Syrjänen ◽  
Luca Pellegrini ◽  
Owen Richard Davies
Keyword(s):  
Molecular Model ◽  
Meiotic Chromosome ◽  
Lateral Element ◽  
Homologous Chromosomes ◽  
Meiotic Chromosomes ◽  
Double Stranded Dna ◽  
Evolutionarily Conserved ◽  
20 Nm ◽  
Chromosome Organisation

The synaptonemal complex (SC) is an evolutionarily-conserved protein assembly that holds together homologous chromosomes during prophase of the first meiotic division. Whilst essential for meiosis and fertility, the molecular structure of the SC has proved resistant to elucidation. The SC protein SYCP3 has a crucial but poorly understood role in establishing the architecture of the meiotic chromosome. Here we show that human SYCP3 forms a highly-elongated helical tetramer of 20 nm length. N-terminal sequences extending from each end of the rod-like structure bind double-stranded DNA, enabling SYCP3 to link distant sites along the sister chromatid. We further find that SYCP3 self-assembles into regular filamentous structures that resemble the known morphology of the SC lateral element. Together, our data form the basis for a model in which SYCP3 binding and assembly on meiotic chromosomes leads to their organisation into compact structures compatible with recombination and crossover formation.

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.

scholarly journals Mad2-independent Spindle Assembly Checkpoint Activation and Controlled Metaphase–Anaphase Transition inDrosophilaS2 Cells

2007 ◽  
Vol 18 (3) ◽  
pp. 850-863 ◽  
Author(s):  
Bernardo Orr ◽  
Hassan Bousbaa ◽  
Claudio E. Sunkel
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Mitotic Progression ◽  
Experimental Conditions ◽  
Checkpoint Activation ◽  
Nuclear Envelope Breakdown ◽  
Chromatin Bridges ◽  
Delay Progression

The spindle assembly checkpoint is essential to maintain genomic stability during cell division. We analyzed the role of the putative Drosophila Mad2 homologue in the spindle assembly checkpoint and mitotic progression. Depletion of Mad2 by RNAi from S2 cells shows that it is essential to prevent mitotic exit after spindle damage, demonstrating its conserved role. Mad2-depleted cells also show accelerated transit through prometaphase and premature sister chromatid separation, fail to form metaphases, and exit mitosis soon after nuclear envelope breakdown with extensive chromatin bridges that result in severe aneuploidy. Interestingly, preventing Mad2-depleted cells from exiting mitosis by a checkpoint-independent arrest allows congression of normally condensed chromosomes. More importantly, a transient mitotic arrest is sufficient for Mad2-depleted cells to exit mitosis with normal patterns of chromosome segregation, suggesting that all the associated phenotypes result from a highly accelerated exit from mitosis. Surprisingly, if Mad2-depleted cells are blocked transiently in mitosis and then released into a media containing a microtubule poison, they arrest with high levels of kinetochore-associated BubR1, properly localized cohesin complex and fail to exit mitosis revealing normal spindle assembly checkpoint activity. This behavior is specific for Mad2 because BubR1-depleted cells fail to arrest in mitosis under these experimental conditions. Taken together our results strongly suggest that Mad2 is exclusively required to delay progression through early stages of prometaphase so that cells have time to fully engage the spindle assembly checkpoint, allowing a controlled metaphase–anaphase transition and normal patterns of chromosome segregation.

scholarly journals Maintenance DNA methylation in pre-meiotic germ cells regulates meiotic prophase by facilitating homologous chromosome pairing

Development ◽  
2021 ◽  
Vol 148 (10) ◽  
Author(s):  
Yuki Takada ◽  
Ruken Yaman-Deveci ◽  
Takayuki Shirakawa ◽  
Jafar Sharif ◽  
Shin-ichi Tomizawa ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Cells ◽  
Meiotic Prophase ◽  
De Novo ◽  
Pericentric Heterochromatin ◽  
Male Germ Cells ◽  
Homologous Chromosomes ◽  
Homologous Chromosome Pairing ◽  
Synaptic Failure

ABSTRACT Heterochromatin-related epigenetic mechanisms, such as DNA methylation, facilitate pairing of homologous chromosomes during the meiotic prophase of mammalian spermatogenesis. In pro-spermatogonia, de novo DNA methylation plays a key role in completing meiotic prophase and initiating meiotic division. However, the role of maintenance DNA methylation in the regulation of meiosis, especially in the adult, is not well understood. Here, we reveal that NP95 (also known as UHRF1) and DNMT1 – two essential proteins for maintenance DNA methylation – are co-expressed in spermatogonia and are necessary for meiosis in male germ cells. We find that Np95- or Dnmt1-deficient spermatocytes exhibit spermatogenic defects characterized by synaptic failure during meiotic prophase. In addition, assembly of pericentric heterochromatin clusters in early meiotic prophase, a phenomenon that is required for subsequent pairing of homologous chromosomes, is disrupted in both mutants. Based on these observations, we propose that DNA methylation, established in pre-meiotic spermatogonia, regulates synapsis of homologous chromosomes and, in turn, quality control of male germ cells. Maintenance DNA methylation, therefore, plays a role in ensuring faithful transmission of both genetic and epigenetic information to offspring.

scholarly journals Micromanipulation of prophase I chromosomes from mouse spermatocytes reveals high stiffness and gel-like chromatin organization

2020 ◽  
Author(s):  
Ronald Biggs ◽  
Ning Liu ◽  
Yiheng Peng ◽  
John F. Marko ◽  
Huanyu Qiao
Keyword(s):  
Meiotic Prophase ◽  
Central Element ◽  
Critical Event ◽  
Mitotic Chromosomes ◽  
Large Protein ◽  
Homologous Chromosomes ◽  
Prophase I ◽  
Meiotic Prophase I ◽  
Meiotic Chromosomes ◽  
Genetic Mutants

Meiosis produces four haploid cells after two successive divisions in sexually reproducing organisms. A critical event during meiosis is construction of the synaptonemal complex (SC), a large, protein-based bridge that physically links homologous chromosomes. The SC facilitates meiotic recombination, chromosome compaction, and the eventual separation of homologous chromosomes at metaphase I. We present experiments directly measuring physical properties of captured mammalian meiotic prophase I chromosomes. Mouse meiotic chromosomes are about ten-fold stiffer than somatic mitotic chromosomes, even for genetic mutants lacking SYCP1, the central element of the SC. Meiotic chromosomes dissolve when treated with nucleases, but only weaken when treated with proteases, suggesting that the SC is not rigidly connected, and that meiotic prophase I chromosomes are a gel meshwork of chromatin, similar to mitotic chromosomes. These results are consistent with a liquid- or liquid-crystal SC, but with SC-chromatin stiff enough to mechanically drive crossover interference.

scholarly journals Epigenetic inheritance of centromere identity in a heterologous system

2019 ◽  
Author(s):  
Virginie Roure ◽  
Bethan Medina-Pritchard ◽  
Eduard Anselm ◽  
A. Arockia Jeyaprakash ◽  
Patrick Heun
Keyword(s):  
Chromosome Segregation ◽  
Chromosomal Region ◽  
Histone H3 ◽  
Epigenetic Inheritance ◽  
Centromeric Chromatin ◽  
Centromere Proteins ◽  
Heterologous System ◽  
Histone H3 Variant ◽  
Self Association

SUMMARYThe centromere is an essential chromosomal region required for accurate chromosome segregation. Most eukaryotic centromeres are defined epigenetically by the histone H3 variant, CENP-A, yet how its self-propagation is achieved remains poorly understood. Here we developed a heterologous system to reconstitute epigenetic inheritance of centromeric chromatin by ectopically targeting the Drosophila centromere proteins dCENP-A, dCENP-C and CAL1 to LacO arrays in human cells. Dissecting the function of these three components uncovers the key role of self-association of dCENP-C and CAL1 for their mutual interaction and dCENP-A deposition. Importantly, we identify the components required for dCENP-C loading onto chromatin, involving a cooperation between CAL1 and dCENP-A nucleosomes, thus closing the epigenetic loop to ensure dCENP-C and dCENP-A replenishment during the cell division cycle. Finally, we show that all three Drosophila factors are sufficient for dCENP-A propagation and propose a model for the epigenetic inheritance of centromere identity.

scholarly journals The kinetochore prevents centromere-proximal crossover recombination during meiosis

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Nadine Vincenten ◽  
Lisa-Marie Kuhl ◽  
Isabel Lam ◽  
Ashwini Oke ◽  
Alastair RW Kerr ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Trisomy 21 ◽  
Budding Yeast ◽  
Dna Breaks ◽  
Homologous Chromosomes ◽  
Increased Risk ◽  
Dna Break ◽  
Break Formation

During meiosis, crossover recombination is essential to link homologous chromosomes and drive faithful chromosome segregation. Crossover recombination is non-random across the genome, and centromere-proximal crossovers are associated with an increased risk of aneuploidy, including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub-complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the Ctf19 complex, operating across distinct chromosomal distances. The Ctf19 complex prevents meiotic DNA break formation, the initiating event of recombination, proximal to the centromere. The Ctf19 complex independently drives the enrichment of cohesin throughout the broader pericentromere to suppress crossovers, but not DNA breaks. This non-canonical role of the kinetochore in defining a chromosome domain that is refractory to crossovers adds a new layer of functionality by which the kinetochore prevents the incidence of chromosome segregation errors that generate aneuploid gametes.

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