FBXO47 is essential for preventing the synaptonemal complex from premature disassembly in mouse male meiosis

Meiotic prophase is a prolonged G2 phase that ensures the completion of numerous meiosis-specific chromosome events. During meiotic prophase, homologous chromosomes undergo synapsis to facilitate meiotic recombination yielding crossovers. It remains largely elusive how homolog synapsis is temporally maintained and destabilized during meiotic prophase. Here we show that FBXO47 is the stabilizer of synaptonemal complex during male meiotic prophase. Disruption of FBXO47 shows severe impact on homologous chromosome synapsis and DSB repair processes, leading to male infertility. Notably, in the absence of FBXO47, although once homologous chromosomes are synapsed, the synaptonemal complex is precociously disassembled before progressing beyond pachytene. Remarkably, Fbxo47 KO spermatocytes remain in earlier stage of meiotic prophase and lack crossovers, despite apparently exhibiting diplotene-like chromosome morphology. We propose that FBXO47 functions independently of SCF E3 ligase, and plays a crucial role in preventing synaptonemal complex from premature disassembly during cell cycle progression of meiotic prophase.

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Lateral Elements Inside Synaptonemal Complex-Like Polycomplexes in ndt80 Mutants of Yeast Bind DNA

Genetics ◽

10.1093/genetics/163.2.539 ◽

2003 ◽

Vol 163 (2) ◽

pp. 539-544 ◽

Cited By ~ 1

Author(s):

Hasanuzzaman Bhuiyan ◽

Gunilla Dahlfors ◽

Karin Schmekel

Keyword(s):

In Situ Hybridization ◽

Electron Microscope ◽

Synaptonemal Complex ◽

Immunoelectron Microscopy ◽

Meiotic Prophase ◽

Lateral Element ◽

Homologous Chromosomes ◽

Meiotic Prophase I ◽

Dna Antibodies

Abstract The synaptonemal complex (SC) keeps the synapsed homologous chromosomes together during pachytene in meiotic prophase I. Structures that resemble stacks of SCs, polycomplexes, are sometimes found before or after pachytene. We have investigated ndt80 mutants of yeast, which arrest in pachytene. SCs appear normal in spread chromosome preparations, but are only occasionally found in intact nuclei examined in the electron microscope. Instead, large polycomplexes occur in almost every ndt80 mutant nucleus. Immunoelectron microscopy using DNA antibodies show strong preferential labeling to the lateral element parts of the polycomplexes. In situ hybridization using chromosome-specific probes confirms that the chromosomes in ndt80 mutants are paired and attached to the SCs. Our results suggest that polycomplexes can be involved in binding of chromosomes and possibly also in synapsis.

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Simian virus 40 compensates a cellular mutational defect of a serum-dependent function controlling cell cycle progression in the G2 phase

Virology ◽

10.1016/0042-6822(88)90632-0 ◽

1988 ◽

Vol 164 (1) ◽

pp. 165-170 ◽

Cited By ~ 1

Author(s):

Hirokazu Zaitsu ◽

Genki Kimura

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Simian Virus 40 ◽

Simian Virus ◽

Cycle Progression ◽

Dependent Function ◽

G2 Phase ◽

Serum Dependent

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Distinct prophase arrest mechanisms in human male meiosis

10.1101/195321 ◽

2017 ◽

Author(s):

Sabrina Z. Jan ◽

Aldo Jongejan ◽

Cindy M. Korver ◽

Saskia K. M. van Daalen ◽

Ans M. M. van Pelt ◽

...

Keyword(s):

Genomic Stability ◽

Male Meiosis ◽

Type I ◽

Type Ii ◽

Meiotic Arrest ◽

Homologous Chromosomes ◽

Xy Body ◽

Chromosome Synapsis ◽

Human Male ◽

Meiotic Crossover

To prevent chromosomal aberrations to be transmitted to the offspring, strict meiotic checkpoints are in place to remove aberrant spermatocytes. However, in about 1% of all males these checkpoints cause complete meiotic arrest leading to azoospermia and subsequent infertility. We here unravel two clearly distinct meiotic arrest mechanisms that act during the 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 ZFY and seem to activate a DNA damage pathway leading to induction of p63 mediated spermatocyte elimination. 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 properly silence the X-chromosome encoded gene ZFX. Discovery and understanding of these meiotic arrest mechanisms increases our knowledge on how genomic stability is guarded during human germ cell development.

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Cubic Membranes Formation in Synchronized Human Hepatocellular Carcinoma Cells Reveals a Possible Role as a Structural Antioxidant Defense System in Cell Cycle Progression

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.617406 ◽

2020 ◽

Vol 8 ◽

Author(s):

Deqin Kong ◽

Rui Liu ◽

Jiangzheng Liu ◽

Qingbiao Zhou ◽

Jiaxin Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle ◽

Cell Cycle Progression ◽

S Phase ◽

Carcinoma Cells ◽

Human Hepatocellular Carcinoma ◽

Cycle Progression ◽

Hepatocellular Carcinoma Cells ◽

G2 Phase ◽

Human Hepatocellular Carcinoma Cells

Cubic membranes (CMs) represent unique biological membrane structures with highly curved three-dimensional periodic minimal surfaces, which have been observed in a wide range of cell types and organelles under various stress conditions (e. g., starvation, virus-infection, and oxidation). However, there are few reports on the biological roles of CMs, especially their roles in cell cycle. Hence, we established a stable cell population of human hepatocellular carcinoma cells (HepG2) of 100% S phase by thymidine treatment, and determined certain parameters in G2 phase released from S phase. Then we found a close relationship between CMs formation and cell cycle, and an increase in reactive oxygen species (ROS) and mitochondrial function. After the synchronization of HepG2 cells were induced, CMs were observed through transmission electron microscope in G2 phase but not in G1, S and M phase. Moreover, the increased ATP production, mitochondrial and intracellular ROS levels were also present in G2 phase, which demonstrated a positive correlation with CMs formation by Pearson correlation analysis. This study suggests that CMs may act as an antioxidant structure in response to mitochondria-derived ROS during G2 phase and thus participate in cell cycle progression.

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DNA Damage during G2 Phase Does Not Affect Cell Cycle Progression of the Green Alga Scenedesmus quadricauda

PLoS ONE ◽

10.1371/journal.pone.0019626 ◽

2011 ◽

Vol 6 (5) ◽

pp. e19626 ◽

Cited By ~ 10

Author(s):

Monika Hlavová ◽

Mária Čížková ◽

Milada Vítová ◽

Kateřina Bišová ◽

Vilém Zachleder

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Green Alga ◽

Cell Cycle Progression ◽

Scenedesmus Quadricauda ◽

Cycle Progression ◽

Affect Cell Cycle Progression ◽

G2 Phase ◽

Alga Scenedesmus Quadricauda

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

Molecular Biology of the Cell ◽

10.1091/mbc.e12-11-0841 ◽

2013 ◽

Vol 24 (7) ◽

pp. 1053-1067 ◽

Cited By ~ 25

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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HIV-1 Vif promotes the G1- to S-phase cell-cycle transition

Blood ◽

10.1182/blood-2010-06-289215 ◽

2011 ◽

Vol 117 (4) ◽

pp. 1260-1269 ◽

Cited By ~ 18

Author(s):

Jiangfang Wang ◽

Emma L. Reuschel ◽

Jason M. Shackelford ◽

Lauren Jeang ◽

Debra K. Shivers ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

S Phase ◽

Phase Cell ◽

Small Interfering Rnas ◽

Cycle Progression ◽

Viral Infectivity Factor ◽

G2 Phase ◽

Regulate Cell Cycle Progression ◽

Hiv 1

AbstractHIV-1 depends on host-cell resources for replication, access to which may be limited to a particular phase of the cell cycle. The HIV-encoded proteins Vpr (viral protein R) and Vif (viral infectivity factor) arrest cells in the G2 phase; however, alteration of other cell-cycle phases has not been reported. We show that Vif drives cells out of G1 and into the S phase. The effect of Vif on the G1-to-S transition is distinct from its effect on G2, because G2 arrest is Cullin5-dependent, whereas the G1-to-S progression is Cullin5-independent. Using mass spectrometry, we identified 2 novel cellular partners of Vif, Brd4 and Cdk9, both of which are known to regulate cell-cycle progression. We confirmed the interaction of Vif and Cdk9 by immunoprecipitation and Western blot, and showed that small interfering RNAs (siRNAs) specific for Cdk9 inhibit the Vif-mediated G1-to-S transition. These data suggest that Vif regulates early cell-cycle progression, with implications for infection and latency.

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The apparent requirement for protein synthesis during G2 phase is due to checkpoint activation

10.1101/863548 ◽

2019 ◽

Author(s):

Sarah Lockhead ◽

Alisa Moskaleva ◽

Julia Kamenz ◽

Yuxin Chen ◽

Minjung Kang ◽

...

Keyword(s):

Protein Synthesis ◽

P38 Mapk ◽

Cell Cycle Progression ◽

Kinase Inhibitor ◽

Protein Synthesis Inhibitors ◽

Checkpoint Activation ◽

Cycle Progression ◽

Mitotic Entry ◽

M Phase ◽

G2 Phase

AbstractProtein synthesis inhibitors (e.g. cycloheximide) prevent cells from entering mitosis, suggesting that cell cycle progression requires protein synthesis until right before mitotic entry. However, cycloheximide is also known to activate p38 MAPK, which can delay mitotic entry through a G2/M checkpoint. Here we asked whether checkpoint activation or a requirement for protein synthesis is responsible for the cycloheximide effect. We found that p38 inhibitors prevent cycloheximide-treated cells from arresting in G2 phase, and that G2 duration is normal in about half of these cells. The Wee1/Myt1 inhibitor PD0166285 also prevents cycloheximide from blocking mitotic entry, raising the possibility that Wee1 and/or Myt1 mediate the cycloheximide-induced G2 arrest. Thus, the ultimate trigger for mitotic entry appears not to be the continued synthesis of mitotic cyclins or other proteins. However, M-phase progression was delayed in cycloheximide-plus-kinase-inhibitor-treated cells, emphasizing the different requirements of protein synthesis for timely entry and completion of mitosis.Impact statementCycloheximide arrests cells in G2 phase due to activation of p38 MAPK, not inhibition of protein synthesis, arguing that protein synthesis in G2 phase is not required for mitotic entry.

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Repurposing of Synaptonemal Complex Proteins for Kinetochores in Kinetoplastida

10.1101/2021.02.06.430040 ◽

2021 ◽

Cited By ~ 1

Author(s):

Eelco C. Tromer ◽

Thomas A. Wemyss ◽

Ross F. Waller ◽

Bungo Akiyoshi

Keyword(s):

Gene Family ◽

Synaptonemal Complex ◽

Chromosome Segregation ◽

Homology Detection ◽

Homologous Chromosomes ◽

Chromosome Synapsis ◽

Core Set ◽

History Of ◽

Macromolecular Protein ◽

Axial Element

AbstractChromosome segregation in eukaryotes is driven by a macromolecular protein complex called the kinetochore that connects centromeric DNA to microtubules of the spindle apparatus. Kinetochores in well-studied model eukaryotes consist of a core set of proteins that are broadly conserved among distant eukaryotic phyla. In contrast, unicellular flagellates of the class Kinetoplastida have a unique set of kinetochore components. The evolutionary origin and history of these kinetochores remains unknown. Here, we report evidence of homology between three kinetoplastid kinetochore proteins KKT16–18 and axial element components of the synaptonemal complex, such as the SYCP2:SYCP3 multimers found in vertebrates. The synaptonemal complex is a zipper-like structure that assembles between homologous chromosomes during meiosis to promote recombination. Using a sensitive homology detection protocol, we identify divergent orthologues of SYCP2:SYCP3 in most eukaryotic supergroups including other experimentally established axial element components, such as Red1 and Rec10 in budding and fission yeast, and the ASY3:ASY4 multimers in land plants. These searches also identify KKT16–18 as part of this rapidly evolving protein family. The widespread presence of the SYCP2-3 gene family in extant eukaryotes suggests that the synaptonemal complex was likely present in the last eukaryotic common ancestor. We found at least twelve independent duplications of the SYCP2-3 gene family throughout the eukaryotic tree of life, providing opportunities for new functional complexes to arise, including KKT16–18 in Trypanosoma brucei. We propose that kinetoplastids evolved their unique kinetochore system by repurposing meiotic components of the chromosome synapsis and homologous recombination machinery that were already present in early eukaryotes.

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