scholarly journals Wapl releases Scc1-cohesin and regulates chromosome structure and segregation in mouse oocytes

2020 ◽  
Vol 219 (4) ◽  
Author(s):  
Mariana C.C. Silva ◽  
Sean Powell ◽  
Sabrina Ladstätter ◽  
Johanna Gassler ◽  
Roman Stocsits ◽  
...  
Keyword(s):  
Residence Time ◽  
Chromosome Segregation ◽  
Chromosome Structure ◽  
Somatic Cells ◽  
Cell Types ◽  
Chromosome Organization ◽  
Loop Size ◽  
Mouse Oocytes ◽  
Single Nucleus ◽  
Meiosis I

Cohesin is essential for genome folding and inheritance. In somatic cells, these functions are both mediated by Scc1-cohesin, which in mitosis is released from chromosomes by Wapl and separase. In mammalian oocytes, cohesion is mediated by Rec8-cohesin. Scc1 is expressed but neither required nor sufficient for cohesion, and its function remains unknown. Likewise, it is unknown whether Wapl regulates one or both cohesin complexes and chromosome segregation in mature oocytes. Here, we show that Wapl is required for accurate meiosis I chromosome segregation, predominantly releases Scc1-cohesin from chromosomes, and promotes production of euploid eggs. Using single-nucleus Hi-C, we found that Scc1 is essential for chromosome organization in oocytes. Increasing Scc1 residence time on chromosomes by Wapl depletion leads to vermicelli formation and intra-loop structures but, unlike in somatic cells, does not increase loop size. We conclude that distinct cohesin complexes generate loops and cohesion in oocytes and propose that the same principle applies to all cell types and species.

scholarly journals Aurora-C Kinase Deficiency Causes Cytokinesis Failure in Meiosis I and Production of Large Polyploid Oocytes in Mice

2010 ◽  
Vol 21 (14) ◽  
pp. 2371-2383 ◽  
Author(s):  
Kuo-Tai Yang ◽  
Shu-Kuei Li ◽  
Chih-Chieh Chang ◽  
Chieh-Ju C. Tang ◽  
Yi-Nan Lin ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Female Mouse ◽  
Histone H3 ◽  
Aurora B ◽  
Binding Motif ◽  
Mouse Oocytes ◽  
Microtubule Attachment ◽  
H3 Phosphorylation ◽  
Histone H3 Phosphorylation ◽  
Meiosis I

We previously isolated Aurora-C/Aie1 in a screen for kinases expressed in mouse sperm and eggs. Here, we show the localization of endogenous Aurora-C and examine its roles during female mouse meiosis. Aurora-C was detected at the centromeres and along the chromosome arms in prometaphase I–metaphase I and was concentrated at centromeres at metaphase II, in which Aurora-C also was phosphorylated at Thr171. During the anaphase I–telophase I transition, Aurora-C was dephosphorylated and relocalized to the midzone and midbody. Microinjection of the kinase-deficient Aurora-C (AurC-KD) mRNA into mouse oocytes significantly inhibited Aurora-C activity and caused multiple defects, including chromosome misalignment, abnormal kinetochore–microtubule attachment, premature chromosome segregation, and cytokinesis failure in meiosis I. Furthermore, AurC-KD reduced Aurora-C and histone H3 phosphorylation and inhibited kinetochore localization of Bub1 and BubR1. Similar effects also were observed in the oocytes injected with INCNEP-delIN mRNAs, in which the Aurora-C binding motif was removed. The most dramatic effect observed in AurC-KD–injected oocytes is cytokinesis failure in meiosis I, resulting in producing large polyploid oocytes, a pattern similar to Aurora-C deficiency human spermatozoa. Surprisingly, we detected no Aurora-B protein in mouse oocytes. We propose that Aurora-C, but not Aurora-B, plays essential roles in female mouse meiosis.

scholarly journals Chromosome remodelling by SMC/Condensin in B. subtilis is regulated by Soj/ParA during growth and sporulation

2021 ◽  
Author(s):  
David M Roberts ◽  
Anna Anchimiuk ◽  
Tomas G Kloosterman ◽  
Heath Murray ◽  
Ling Juan Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bacillus Subtilis ◽  
Chromosome Segregation ◽  
Chromosome Structure ◽  
Replication Initiation ◽  
Chromosome Organization ◽  
Filament Formation ◽  
Axial Filament ◽  
Dna Replication Initiation ◽  
The Web

SMC complexes, loaded at ParB-parS sites, are key mediators of chromosome organization in bacteria. ParA/Soj proteins interact with ParB/Spo0J in a pathway involving ATP-dependent dimerization and DNA binding, leading to chromosome segregation and SMC loading. In Bacillus subtilis, ParA/Soj also regulates DNA replication initiation, and along with ParB/Spo0J is involved in cell cycle changes during endospore formation. The first morphological stage in sporulation is the formation of an elongated chromosome structure called an axial filament. We now show that a major redistribution of SMC complexes drives axial filament formation, in a process regulated by ParA/Soj. Unexpectedly, this regulation is dependent on monomeric forms of ParA/Soj that cannot bind DNA or hydrolyse ATP. These results reveal a new role for ParA/Soj proteins in the regulation of SMC dynamics in bacteria, and yet further complexity in the web of interactions involving chromosome replication, segregation, and organization, controlled by ParAB and SMC.

scholarly journals PLK1 is required for chromosome compaction and microtubule organization in mouse oocytes

2020 ◽  
Vol 31 (12) ◽  
pp. 1206-1217
Author(s):  
Tara M. Little ◽  
Philip W. Jordan
Keyword(s):  
Chromosome Segregation ◽  
Microtubule Organizing Center ◽  
Microtubule Organization ◽  
Spindle Formation ◽  
Bipolar Spindle ◽  
Mouse Oocytes ◽  
Organizing Center ◽  
Meiosis I

By deleting Plk1 in mouse oocytes before meiotic resumption, we show that PLK1 is essential for the formation of condensed bivalent chromosomes, microtubule organizing center fragmentation, liquid-like spindle domain localization, and bipolar spindle formation. Thus, PLK1 coordinates processes that ensure chromosome segregation during meiosis I.

scholarly journals Distinct classes of lagging chromosome underpin age-related oocyte aneuploidy in mouse

2021 ◽  
Author(s):  
Aleksandar I. Mihajlović ◽  
Jenna Haverfield ◽  
Greg FitzHarris
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Maternal Age ◽  
Class Ii ◽  
Class I ◽  
Mouse Oocytes ◽  
Age Related ◽  
Lagging Chromosome ◽  
Segregation Phenomenon ◽  
Meiosis I

SUMMARYChromosome segregation errors that cause oocyte aneuploidy increase in frequency with maternal age and are considered a major contributing factor of age-related fertility decline in females. A common age-associated chromosome segregation phenomenon in oocytes is the lagging anaphase chromosome, but whether anaphase laggards actually missegregate and cause aneuploidy is unclear. Here we show unexpectedly that lagging chromosomes in mouse oocytes comprise two mechanistically distinct classes of motion that we refer to as ‘Class-I’ and ‘Class-II’. We use imaging approaches and mechanistic interventions to dissociate the two classes, and find that whereas Class-II laggards are benign, Class-I laggards can directly cause aneuploidy. Most notably, a controlled prolongation of meiosis-I specifically lessens Class-I lagging to prevent aneuploidy. Our data thus reveal lagging chromosomes to be a cause of age-related aneuploidy in mouse oocytes and suggest that manipulating the cell cycle could increase the yield of useful oocytes in some contexts.

scholarly journals A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Christopher Thomas ◽  
Benjamin Wetherall ◽  
Mark D. Levasseur ◽  
Rebecca J. Harris ◽  
Scott T. Kerridge ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Chromosome Segregation ◽  
Cell Cycle Proteins ◽  
Meiotic Progression ◽  
Mouse Oocytes ◽  
Destruction Mechanism ◽  
Meiosis I

AbstractSuccessful cell division relies on the timely removal of key cell cycle proteins such as securin. Securin inhibits separase, which cleaves the cohesin rings holding chromosomes together. Securin must be depleted before anaphase to ensure chromosome segregation occurs with anaphase. Here we find that in meiosis I, mouse oocytes contain an excess of securin over separase. We reveal a mechanism that promotes excess securin destruction in prometaphase I. Importantly, this mechanism relies on two phenylalanine residues within the separase-interacting segment (SIS) of securin that are only exposed when securin is not bound to separase. We suggest that these residues facilitate the removal of non-separase-bound securin ahead of metaphase, as inhibiting this period of destruction by mutating both residues causes the majority of oocytes to arrest in meiosis I. We further propose that cellular securin levels exceed the amount an oocyte is capable of removing in metaphase alone, such that the prometaphase destruction mechanism identified here is essential for correct meiotic progression in mouse oocytes.

Meiotic CENP-C is a shepherd: bridging the space between the centromere and the kinetochore in time and space

2020 ◽  
Vol 64 (2) ◽  
pp. 251-261
Author(s):  
Jessica E. Fellmeth ◽  
Kim S. McKim
Keyword(s):  
Chromosome Segregation ◽  
New Technologies ◽  
Early Prophase ◽  
Unique Role ◽  
Kinetochore Assembly ◽  
M Phase ◽  
In Vivo Analysis ◽  
Meiosis I

Abstract While many of the proteins involved in the mitotic centromere and kinetochore are conserved in meiosis, they often gain a novel function due to the unique needs of homolog segregation during meiosis I (MI). CENP-C is a critical component of the centromere for kinetochore assembly in mitosis. Recent work, however, has highlighted the unique features of meiotic CENP-C. Centromere establishment and stability require CENP-C loading at the centromere for CENP-A function. Pre-meiotic loading of proteins necessary for homolog recombination as well as cohesion also rely on CENP-C, as do the main scaffolding components of the kinetochore. Much of this work relies on new technologies that enable in vivo analysis of meiosis like never before. Here, we strive to highlight the unique role of this highly conserved centromere protein that loads on to centromeres prior to M-phase onset, but continues to perform critical functions through chromosome segregation. CENP-C is not merely a structural link between the centromere and the kinetochore, but also a functional one joining the processes of early prophase homolog synapsis to late metaphase kinetochore assembly and signaling.

scholarly journals Genetic analysis of amyotrophic lateral sclerosis identifies contributing pathways and cell types

2021 ◽  
Vol 7 (3) ◽  
pp. eabd9036
Author(s):  
Sara Saez-Atienzar ◽  
Sara Bandres-Ciga ◽  
Rebekah G. Langston ◽  
Jonggeol J. Kim ◽  
Shing Wan Choi ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Polygenic Risk Score ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Data Driven Approach ◽  
Single Nucleus ◽  
Lateral Sclerosis

Despite the considerable progress in unraveling the genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand the molecular mechanisms underlying the disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify the biological pathways and cell types involved in ALS. This data-driven approach identified multiple aspects of the biology underlying the disease that resolved into broader themes, namely, neuron projection morphogenesis, membrane trafficking, and signal transduction mediated by ribonucleotides. We also found that genomic risk in ALS maps consistently to GABAergic interneurons and oligodendrocytes, as confirmed in human single-nucleus RNA-seq data. Using two-sample Mendelian randomization, we nominated six differentially expressed genes (ATG16L2, ACSL5, MAP1LC3A, MAPKAPK3, PLXNB2, and SCFD1) within the significant pathways as relevant to ALS. We conclude that the disparate genetic etiologies of this fatal neurological disease converge on a smaller number of final common pathways and cell types.

scholarly journals Sequential production of gametes during meiosis in trypanosomes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Lori Peacock ◽  
Chris Kay ◽  
Chloe Farren ◽  
Mick Bailey ◽  
Mark Carrington ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Nuclear Dna ◽  
Nuclear Dna Content ◽  
Cell Types ◽  
Tsetse Fly ◽  
Binucleate Cell ◽  
Insect Vector ◽  
Content Ratio ◽  
Different Cell Types ◽  
Meiosis I

AbstractMeiosis is a core feature of eukaryotes that occurs in all major groups, including the early diverging excavates. In this group, meiosis and production of haploid gametes have been described in the pathogenic protist, Trypanosoma brucei, and mating occurs in the salivary glands of the insect vector, the tsetse fly. Here, we searched for intermediate meiotic stages among trypanosomes from tsetse salivary glands. Many different cell types were recovered, including trypanosomes in Meiosis I and gametes. Significantly, we found trypanosomes containing three nuclei with a 1:2:1 ratio of DNA contents. Some of these cells were undergoing cytokinesis, yielding a mononucleate gamete and a binucleate cell with a nuclear DNA content ratio of 1:2. This cell subsequently produced three more gametes in two further rounds of division. Expression of the cell fusion protein HAP2 (GCS1) was not confined to gametes, but also extended to meiotic intermediates. We propose a model whereby the two nuclei resulting from Meiosis I undergo asynchronous Meiosis II divisions with sequential production of haploid gametes.

scholarly journals Multiple Subunits of the Caenorhabditis elegans Anaphase-Promoting Complex Are Required for Chromosome Segregation During Meiosis I

Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 805-813 ◽  
Author(s):  
Edward S Davis ◽  
Lucia Wille ◽  
Barry A Chestnut ◽  
Penny L Sadler ◽  
Diane C Shakes ◽  
...  
Keyword(s):  
Rna Interference ◽  
Caenorhabditis Elegans ◽  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Anaphase Promoting Complex ◽  
Genetic Screens ◽  
Chromatid Cohesion ◽  
Interference Studies ◽  
Meiosis I

Abstract Two genes, originally identified in genetic screens for Caenorhabditis elegans mutants that arrest in metaphase of meiosis I, prove to encode subunits of the anaphase-promoting complex or cyclosome (APC/C). RNA interference studies reveal that these and other APC/C subunits are essential for the segregation of chromosomal homologs during meiosis I. Further, chromosome segregation during meiosis I requires APC/C functions in addition to the release of sister chromatid cohesion.

scholarly journals Double or nothing: a Drosophila mutation affecting meiotic chromosome segregation in both females and males.

Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 953-964 ◽  
Author(s):  
D P Moore ◽  
W Y Miyazaki ◽  
J E Tomkiel ◽  
T L Orr-Weaver
Keyword(s):  
Cell Death ◽  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Meiotic Chromosome ◽  
Sister Chromatid Cohesion ◽  
Aberrant Chromosome ◽  
Chromatid Cohesion ◽  
Meiotic Nondisjunction ◽  
Lethal Allele ◽  
Meiosis I

Abstract We describe a Drosophila mutation, Double or nothing (Dub), that causes meiotic nondisjunction in a conditional, dominant manner. Previously isolated mutations in Drosophila specifically affect meiosis either in females or males, with the exception of the mei-S332 and ord genes which are required for proper sister-chromatid cohesion. Dub is unusual in that it causes aberrant chromosome segregation almost exclusively in meiosis I in both sexes. In Dub mutant females both nonexchange and exchange chromosomes undergo nondisjunction, but the effect of Dub on nonexchange chromosomes is more pronounced. Dub reduces recombination levels slightly. Multiple nondisjoined chromosomes frequently cosegregate to the same pole. Dub results in nondisjunction of all chromosomes in meiosis I of males, although the levels are lower than in females. When homozygous, Dub is a conditional lethal allele and exhibits phenotypes consistent with cell death.

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