scholarly journals Impact of Global Transcriptional Silencing on Cell Cycle Regulation and Chromosome Segregation in Early Mammalian Embryos

2021 ◽  
Vol 22 (16) ◽  
pp. 9073
Author(s):  
Martin Anger ◽  
Lenka Radonova ◽  
Adela Horakova ◽  
Diana Sekach ◽  
Marketa Charousova
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Significant Proportion ◽  
Transcriptional Silencing ◽  
Early Embryo ◽  
Global Changes ◽  
Embryonic Genome ◽  
Mammalian Embryos ◽  
A Cell ◽  
And Behavior

The onset of an early development is, in mammals, characterized by profound changes of multiple aspects of cellular morphology and behavior. These are including, but not limited to, fertilization and the merging of parental genomes with a subsequent transition from the meiotic into the mitotic cycle, followed by global changes of chromatin epigenetic modifications, a gradual decrease in cell size and the initiation of gene expression from the newly formed embryonic genome. Some of these important, and sometimes also dramatic, changes are executed within the period during which the gene transcription is globally silenced or not progressed, and the regulation of most cellular activities, including those mentioned above, relies on controlled translation. It is known that the blastomeres within an early embryo are prone to chromosome segregation errors, which might, when affecting a significant proportion of a cell within the embryo, compromise its further development. In this review, we discuss how the absence of transcription affects the transition from the oocyte to the embryo and what impact global transcriptional silencing might have on the basic cell cycle and chromosome segregation controlling mechanisms.

scholarly journals Alteration/Deficiency in Activation 3 (ADA3) Protein, a Cell Cycle Regulator, Associates with the Centromere through CENP-B and Regulates Chromosome Segregation

2015 ◽  
Vol 290 (47) ◽  
pp. 28299-28310 ◽  
Author(s):  
Shakur Mohibi ◽  
Shashank Srivastava ◽  
Jun Wang-France ◽  
Sameer Mirza ◽  
Xiangshan Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Protein A ◽  
Cell Cycle Regulator ◽  
A Cell

scholarly journals Micronucleus formation causes perpetual unilateral chromosome inheritance in mouse embryos

2016 ◽  
Vol 113 (3) ◽  
pp. 626-631 ◽  
Author(s):  
Cayetana Vázquez-Diez ◽  
Kazuo Yamagata ◽  
Shardul Trivedi ◽  
Jenna Haverfield ◽  
Greg FitzHarris
Keyword(s):  
Chromosome Segregation ◽  
High Frequency ◽  
Mouse Embryos ◽  
Cell Lineages ◽  
Daughter Cells ◽  
Cell Divisions ◽  
Embryonic Genome ◽  
Mammalian Embryos ◽  
Kinetics Of ◽  
Functional Kinetochore

Chromosome segregation defects in cancer cells lead to encapsulation of chromosomes in micronuclei (MN), small nucleus-like structures within which dangerous DNA rearrangements termed chromothripsis can occur. Here we uncover a strikingly different consequence of MN formation in preimplantation development. We find that chromosomes from within MN become damaged and fail to support a functional kinetochore. MN are therefore not segregated, but are instead inherited by one of the two daughter cells. We find that the same MN can be inherited several times without rejoining the principal nucleus and without altering the kinetics of cell divisions. MN motion is passive, resulting in an even distribution of MN across the first two cell lineages. We propose that perpetual unilateral MN inheritance constitutes an unexpected mode of chromosome missegregation, which could contribute to the high frequency of aneuploid cells in mammalian embryos, but simultaneously may serve to insulate the early embryonic genome from chromothripsis.

Early determination in the C. elegans embryo: a gene, cib-1, required to specify a set of stem-cell-like blastomeres

Development ◽  
1990 ◽  
Vol 108 (1) ◽  
pp. 107-119 ◽  
Author(s):  
R. Schnabel ◽  
H. Schnabel
Keyword(s):  
Cell Cycle ◽  
Decision Making ◽  
Stem Cell ◽  
Early Embryo ◽  
Cell Cycles ◽  
C Elegans ◽  
Lethal Mutations ◽  
A Cell ◽  
Early Decision ◽  
P Cells

The early somatic blastomeres founding the tissues in the C. elegans embryo are derived in a stem-cell-like lineage from the P cells. We have isolated maternal effect lethal mutations defining the gene cib-1 in which the P cells, P1-P3, skip a cell cycle and acquire the fates of only their somatic daughters. Therefore, the cib-1 gene is required for the specification of the stem-cell-like fate of these cells. The analysis of the development of these mutants suggests that the clock controlling the cell cycles in the early embryo is directly coupled to the fate of a cell and that there must be another developmental clock that activates the determinative inventory for the early decision-making.

Dynamic cell cycle-dependent phosphorylation modulates CENP-L-CENP-N centromere recruitment

2021 ◽  
Author(s):  
Alexandra P Navarro ◽  
Iain M Cheeseman
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
S Phase ◽  
Dependent Manner ◽  
Dynamic Cell ◽  
A Cell ◽  
Cycle Dependent ◽  
Unique Cell ◽  
Localization Behavior ◽  
Constitutive Phosphorylation

The kinetochore is a macromolecular structure that is required to ensure proper chromosome segregation during each cell division. The kinetochore is assembled upon a platform of the 16-subunit Constitutive Centromere Associated Network (CCAN), which is present at centromeres throughout the cell cycle. The nature and regulation of CCAN assembly, interactions, and dynamics required to facilitate changing centromere properties and requirements remain to be fully elucidated. The CENP-LN CCAN sub-complex displays a unique cell cycle-dependent localization behavior, peaking in S phase. Here, we demonstrate that phosphorylation of CENP-L and CENP-N controls CENP-LN complex formation and localization in a cell cycle-dependent manner. Mimicking constitutive phosphorylation of either CENP-L or CENP-N or simultaneously preventing phosphorylation of both proteins prevents CENP-LN localization and disrupts chromosome segregation. Together, our work suggests that cycles of phosphorylation and dephosphorylation are critical for CENP-LN complex recruitment and dynamics at centromeres to enable cell cycle-dependent CCAN reorganization.

Abstract 2719: ADA3, a cell cycle regulator, regulates chromosome segregation

2016 ◽  
Author(s):  
Shashank Srivastava ◽  
Shakur Mohibi ◽  
June Wang-France ◽  
Sameer Mirza ◽  
Xiangshan Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Cell Cycle Regulator ◽  
A Cell

scholarly journals Concurrent processes setE. colicell division

2018 ◽  
Vol 4 (11) ◽  
pp. eaau3324 ◽  
Author(s):  
Gabriele Micali ◽  
Jacopo Grilli ◽  
Matteo Osella ◽  
Marco Cosentino Lagomarsino
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Single Cell ◽  
Chromosome Segregation ◽  
Genetic Material ◽  
Replication Initiation ◽  
Concurrent Processes ◽  
A Cell ◽  
Rate Limiting ◽  
Cell Data

A cell can divide only upon completion of chromosome segregation; otherwise, its daughters would lose genetic material. However, we do not know whether the partitioning of chromosomes is the key event for the decision to divide. We show how key trends in single-cell data reject the classic idea of replication-segregation as the rate-limiting process for cell division. Instead, the data agree with a model where two concurrent processes (setting replication initiation and interdivision time) set cell division on competing time scales. During each cell cycle, division is set by the slowest process (an “AND” gate). The concept of transitions between cell cycle stages as decisional processes integrating multiple inputs instead of cascading from orchestrated steps can affect the way we think of the cell cycle in general.

scholarly journals Conservation of the Centromere/Kinetochore Protein ZW10

1997 ◽  
Vol 138 (6) ◽  
pp. 1289-1301 ◽  
Author(s):  
Daniel A. Starr ◽  
Byron C. Williams ◽  
Zexiao Li ◽  
Bijan Etemad-Moghadam ◽  
R. Kelly Dawe ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Metaphase Plate ◽  
C Elegans ◽  
Anaphase Onset ◽  
A Cell ◽  
Cycle Dependent ◽  
Related Proteins ◽  
Drosophila Cells

Mutations in the essential Drosophila melanogaster gene zw10 disrupt chromosome segregation, producing chromosomes that lag at the metaphase plate during anaphase of mitosis and both meiotic divisions. Recent evidence suggests that the product of this gene, DmZW10, acts at the kinetochore as part of a tension-sensing checkpoint at anaphase onset. DmZW10 displays an intriguing cell cycle–dependent intracellular distribution, apparently moving from the centromere/kinetochore at prometaphase to kinetochore microtubules at metaphase, and back to the centromere/kinetochore at anaphase (Williams, B.C., M. Gatti, and M.L. Goldberg. 1996. J. Cell Biol. 134:1127-1140). We have identified ZW10-related proteins from widely diverse species with divergent centromere structures, including several Drosophilids, Caenorhabditis elegans, Arabidopsis thaliana, Mus musculus, and humans. Antibodies against the human ZW10 protein display a cell cycle–dependent staining pattern in HeLa cells strikingly similar to that previously observed for DmZW10 in dividing Drosophila cells. Injections of C. elegans ZW10 antisense RNA phenocopies important aspects of the mutant phenotype in Drosophila: these include a strong decrease in brood size, suggesting defects in meiosis or germline mitosis, a high percentage of lethality among the embryos that are produced, and the appearance of chromatin bridges at anaphase. These results indicate that at least some aspects of the functional role of the ZW10 protein in ensuring proper chromosome segregation are conserved across large evolutionary distances.

scholarly journals The reverse, but coordinated, roles of Tor2 (TORC1) and Tor1 (TORC2) kinases for growth, cell cycle and separase-mediated mitosis in Schizosaccharomyces pombe

Open Biology ◽  
2011 ◽  
Vol 1 (3) ◽  
pp. 110007 ◽  
Author(s):  
Nobuyasu Ikai ◽  
Norihiko Nakazawa ◽  
Takeshi Hayashi ◽  
Mitsuhiro Yanagida
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Schizosaccharomyces Pombe ◽  
Cell Size ◽  
Chromosome Segregation ◽  
Kinase Activity ◽  
Size Control ◽  
Phosphatidyl Inositol ◽  
Nutrient Utilization ◽  
A Cell

Target of rapamycin complexes (TORCs), which are vital for nutrient utilization, contain a catalytic subunit with the phosphatidyl inositol kinase-related kinase (PIKK) motif. TORC1 is required for cell growth, while the functions of TORC2 are less well understood. We show here that the fission yeast Schizosaccharomyces pombe TORC2 has a cell cycle role through determining the proper timing of Cdc2 Tyr15 dephosphorylation and the cell size under limited glucose, whereas TORC1 restrains mitosis and opposes securin–separase, which are essential for chromosome segregation. These results were obtained using the previously isolated TORC1 mutant tor2-L2048S in the phosphatidyl inositol kinase (PIK) domain and a new TORC2 mutant tor1-L2045D , which harbours a mutation in the same site. While mutated TORC1 and TORC2 displayed diminished kinase activity and FKBP12/Fkh1-dependent rapamycin sensitivity, their phenotypes were nearly opposite in mitosis. Premature mitosis and the G2–M delay occurred in TORC1 and TORC2 mutants, respectively. Surprisingly, separase/cut1—securin/cut2 mutants were rescued by TORC1/ tor2-L2048S mutation or rapamycin addition or even Fkh1 deletion, whereas these mutants showed synthetic defect with TORC2/ tor1-L2045D . TORC1 and TORC2 coordinate growth, mitosis and cell size control, such as Wee1 and Cdc25 do for the entry into mitosis.

scholarly journals ISOLATION OF ANEUPLOID-GENERATING MUTANTS OF ASPERGILLUS NIDULANS, ONE OF WHICH IS DEFECTIVE IN INTERPHASE OF THE CELL CYCLE

Genetics ◽  
1984 ◽  
Vol 108 (1) ◽  
pp. 107-121
Author(s):  
A Upshall ◽  
I D Mortimore
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
High Frequency ◽  
Mitotic Chromosome ◽  
Meiotic Chromosome ◽  
Restrictive Temperature ◽  
Single Mutation ◽  
Chromosome Type ◽  
Temperature Exchange ◽  
And Behavior

ABSTRACT A method is described for isolating mutants potentially defective in loci involved in mitotic chromosome segregation. Conditional lethal, heat-sensitive (42°) mutants were assayed at a subrestrictive temperature of 37° for an inflated production of colonies displaying phenotypes and behavior patterns of whole chromosome aneuploids. Of 14 mutants, three showed specificity for one disomic phenotype, whereas 11 generated colonies mosaic for different aneuploid phenotypes. This latter group is designated hfa (high frequency of aneuploid). For ten of the 11 mutants temperature sensitivity and aneuploid production cosegregated, indicating a single mutation in each. These mutations were recessive and nonallelic. Analysis was concentrated on the hfaB3 mutation which is mapped to chromosome VI tightly linked to the methB and tsB loci. The disruptive influence of hfaB3 on mitosis at 37° was shown by (1) ploidy and whole chromosome-type segregation of markers in the breakdown sectors of phenotypically aneuploid colonies obtained from multiply marked homozygous hfaB3 disploids; (2) a high frequency of haploid and nondisjunctional diploid segregants among spontaneous yellow-spored parasexual recombinants taken from green-spored homozygous hfaB3 diploids. The mutation had no effect on meiotic chromosome segregation at 37°. The single interphase nucleus in germlings at 42°, coupled with changes in the mitotic index in temperature exchange experiments, showed hfaB3 to arrest the cell cycle in interphase at restrictive temperature. A conclusion drawn is that the hfaB gene product is required both for entry into mitosis and for normal chromosome segregation in dividing nuclei.

scholarly journals Distinct Developmental Function of Two Caenorhabditis elegans Homologs of the Cohesin Subunit Scc1/Rad21

2003 ◽  
Vol 14 (6) ◽  
pp. 2399-2409 ◽  
Author(s):  
Yoshiko Mito ◽  
Asako Sugimoto ◽  
Masayuki Yamamoto
Keyword(s):  
Cell Cycle ◽  
Caenorhabditis Elegans ◽  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Dependent Manner ◽  
C Elegans ◽  
Late Embryogenesis ◽  
A Cell ◽  
Cohesin Subunit ◽  
Cycle Dependent

Cohesin, which mediates sister chromatid cohesion, is composed of four subunits, named Scc1/Rad21, Scc3, Smc1, and Smc3 in yeast. Caenorhabditis elegans has a single homolog for each of Scc3, Smc1, and Smc3, but as many as four for Scc1/Rad21 (COH-1, SCC-1/COH-2, COH-3, and REC-8). Except for REC-8 required for meiosis, function of these C. elegans proteins remains largely unknown. Herein, we examined their possible involvement in mitosis and development. Embryos depleted of the homolog of either Scc3, or Smc1, or Smc3 by RNA interference revealed a defect in mitotic chromosome segregation but not in chromosome condensation and cytokinesis. Depletion of SCC-1/COH-2 caused similar phenotypes. SCC-1/COH-2 was present in cells destined to divide. It localized to chromosomes in a cell cycle-dependent manner. Worms depleted of COH-1 arrested at either the late embryonic or the larval stage, with no indication of mitotic dysfunction. COH-1 associated chromosomes throughout the cell cycle in all somatic cells undergoing late embryogenesis or larval development. Thus, SCC-1/COH-2 and the homologs of Scc3, Smc1, and Smc3 facilitate mitotic chromosome segregation during the development, presumably by forming a cohesin complex, whereas COH-1 seems to play a role important for development but unrelated to mitosis.

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