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Mechanism of Chromosome Segregation in Eukaryotes

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 26750

Special Issue Editor


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Guest Editor
Graduate School of Integrated Science and Technology, Department of Science, Shizuoka University, Shizuoka, Japan
Interests: meiosis; chromosome segregation; centromere; telomere; sister chromatids; homologous chromosomes; chiasma; kinertochore; microtubule; spindle; dynein; kinesin; MTOC

Special Issue Information

Dear Colleagues,

During the division of a somatic cell (mitosis), duplicated chromosomes (sister chromatids) segregate equally, resulting in the production of two daughter cells that are genetically identical to the original cell. On the other hand, during a series of divisions of a germ cell (meiosis), the segregation of homologous chromosomes and that of sister chromatids sequentially take place, resulting in production of gametes containing half the original number of chromosomes. Chromosome segregation is a complex and dynamic process, and many different events occur. Chromosomes condense, and the bipolar spindle forms. In meiosis, in addition, homologous chromosomes pair and become connected with each other by a recombination product called “chiasma”. Then, the condensed chromosomes interact with the spindle and undergo segregation by moving towards the spindle poles. These events are strictly regulated such that they occur in an ordered manner. Despite the complexity of the segregation process, cells accurately segregate chromosomes in each division and maintain the genome integrity. Once errors occur in chromosome segregation, aneuploidy is generated that is disastrous for cells, and in humans, aneuploidy causes various diseases or disorders including cancers and Down’s syndrome.

Chromosome segregation attracts the interest of many researchers and is being extensively studied in a wide variety of organisms. Recent advances in technology including live cell imaging and single-molecule analysis have greatly improved our understanding of the mechanism of each dynamic event in the chromosome segregation process. This Special Issue on “Mechanism of Chromosome Segregation in Eukaryotes” aims to update our current understanding of the dynamic events in chromosome segregation in mitosis or meiosis and provide an advanced and comprehensive view of the chromosome segregation process. You are warmly invited to submit original research articles and review papers on all subjects related to chromosome segregation including the chromosome structure, sister chromatid cohesion, homologous chromosome pairing, spindle formation, kinetochore functions, and cell cycle regulation. Especially, cutting-edge research articles and thought-provoking reviews are welcome.

Prof. Dr. Ayumu Yamamoto
Guest Editor

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Keywords

  • chromosome segregation
  • mitosis
  • meiosis
  • sister chromatids
  • homologous chromosomes
  • centromere
  • telomere
  • kinetochore
  • spindle
  • MTOC

Published Papers (7 papers)

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Research

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12 pages, 1496 KiB  
Article
Fission Yeast Methylenetetrahydrofolate Reductase Ensures Mitotic and Meiotic Chromosome Segregation Fidelity
by Kim Kiat Lim, Hwei Yee Teo, Yuan Yee Tan, Yi Bing Zeng, Ulysses Tsz Fung Lam, Mahesh Choolani and Ee Sin Chen
Int. J. Mol. Sci. 2021, 22(2), 639; https://doi.org/10.3390/ijms22020639 - 11 Jan 2021
Cited by 6 | Viewed by 2810
Abstract
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate metabolic pathway, and its loss of function through polymorphisms is often associated with human conditions, including cancer, congenital heart disease, and Down syndrome. MTHFR is also required in the maintenance of heterochromatin, a [...] Read more.
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate metabolic pathway, and its loss of function through polymorphisms is often associated with human conditions, including cancer, congenital heart disease, and Down syndrome. MTHFR is also required in the maintenance of heterochromatin, a crucial determinant of genomic stability and precise chromosomal segregation. Here, we characterize the function of a fission yeast gene met11+, which encodes a protein that is highly homologous to the mammalian MTHFR. We show that, although met11+ is not essential for viability, its disruption increases chromosome missegregation and destabilizes constitutive heterochromatic regions at pericentromeric, sub-telomeric and ribosomal DNA (rDNA) loci. Transcriptional silencing at these sites were disrupted, which is accompanied by the reduction in enrichment of histone H3 lysine 9 dimethylation (H3K9me2) and binding of the heterochromatin protein 1 (HP1)-like Swi6. The met11 null mutant also dominantly disrupts meiotic fidelity, as displayed by reduced sporulation efficiency and defects in proper partitioning of the genetic material during meiosis. Interestingly, the faithful execution of these meiotic processes is synergistically ensured by cooperation among Met11, Rec8, a meiosis-specific cohesin protein, and the shugoshin protein Sgo1, which protects Rec8 from untimely cleavage. Overall, our results suggest a key role for Met11 in maintaining pericentromeric heterochromatin for precise genetic inheritance during mitosis and meiosis. Full article
(This article belongs to the Special Issue Mechanism of Chromosome Segregation in Eukaryotes)
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13 pages, 3447 KiB  
Article
N-Terminus Does Not Govern Protein Turnover of Schizosaccharomyces pombe CENP-A
by Hwei Ling Tan, Yi Bing Zeng and Ee Sin Chen
Int. J. Mol. Sci. 2020, 21(17), 6175; https://doi.org/10.3390/ijms21176175 - 26 Aug 2020
Cited by 2 | Viewed by 2256
Abstract
Centromere integrity underlies an essential framework for precise chromosome segregation and epigenetic inheritance. Although centromeric DNA sequences vary among different organisms, all eukaryotic centromeres comprise a centromere-specific histone H3 variant, centromeric protein A (CENP-A), on which other centromeric proteins assemble into the kinetochore [...] Read more.
Centromere integrity underlies an essential framework for precise chromosome segregation and epigenetic inheritance. Although centromeric DNA sequences vary among different organisms, all eukaryotic centromeres comprise a centromere-specific histone H3 variant, centromeric protein A (CENP-A), on which other centromeric proteins assemble into the kinetochore complex. This complex connects chromosomes to mitotic spindle microtubules to ensure accurate partitioning of the genome into daughter cells. Overexpression of CENP-A is associated with many cancers and is correlated with its mistargeting, forming extra-centromeric kinetochore structures. The mislocalization of CENP-A can be counteracted by proteolysis. The amino (N)-terminal domain (NTD) of CENP-A has been implicated in this regulation and shown to be dependent on the proline residues within this domain in Saccharomyces cerevisiae CENP-A, Cse4. We recently identified a proline-rich GRANT motif in the NTD of Schizosaccharomyces pombe CENP-A (SpCENP-A) that regulates the centromeric targeting of CENP-A via binding to the CENP-A chaperone Sim3. Here, we investigated whether the NTD is required to confer SpCENP-A turnover (i.e., counter stability) using various truncation mutants of SpCENP-A. We show that sequential truncation of the NTD did not improve the stability of the protein, indicating that the NTD of SpCENP-A does not drive turnover of the protein. Instead, we reproduced previous observations that heterochromatin integrity is important for SpCENP-A stability, and showed that this occurs in an NTD-independent manner. Cells bearing the null mutant of the histone H3 lysine 9 methyltransferase Clr4 (Δclr4), which have compromised constitutive heterochromatin integrity, showed reductions in the proportion of SpCENP-A in the chromatin-containing insoluble fraction of the cell extract, suggesting that heterochromatin may promote SpCENP-A chromatin incorporation. Thus, a disruption in heterochromatin may result in the delocalization of SpCENP-A from chromatin, thus exposing it to protein turnover. Taken together, we show that the NTD is not required to confer SpCENP-A protein turnover. Full article
(This article belongs to the Special Issue Mechanism of Chromosome Segregation in Eukaryotes)
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15 pages, 3641 KiB  
Article
Genetic Interactions of Histone Modification Machinery Set1 and PAF1C with the Recombination Complex Rec114-Mer2-Mei4 in the Formation of Meiotic DNA Double-Strand Breaks
by Ying Zhang, Takuya Suzuki, Ke Li, Santosh K. Gothwal, Miki Shinohara and Akira Shinohara
Int. J. Mol. Sci. 2020, 21(8), 2679; https://doi.org/10.3390/ijms21082679 - 12 Apr 2020
Cited by 6 | Viewed by 3158
Abstract
Homologous recombination is essential for chromosome segregation during meiosis I. Meiotic recombination is initiated by the introduction of double-strand breaks (DSBs) at specific genomic locations called hotspots, which are catalyzed by Spo11 and its partners. DSB hotspots during meiosis are marked with Set1-mediated [...] Read more.
Homologous recombination is essential for chromosome segregation during meiosis I. Meiotic recombination is initiated by the introduction of double-strand breaks (DSBs) at specific genomic locations called hotspots, which are catalyzed by Spo11 and its partners. DSB hotspots during meiosis are marked with Set1-mediated histone H3K4 methylation. The Spo11 partner complex, Rec114-Mer2-Mei4, essential for the DSB formation, localizes to the chromosome axes. For efficient DSB formation, a hotspot with histone H3K4 methylation on the chromatin loops is tethered to the chromosome axis through the H3K4 methylation reader protein, Spp1, on the axes, which interacts with Mer2. In this study, we found genetic interaction of mutants in a histone modification protein complex called PAF1C with the REC114 and MER2 in the DSB formation in budding yeast Saccharomyces cerevisiae. Namely, the paf1c mutations rtf1 and cdc73 showed synthetic defects in meiotic DSB formation only when combined with a wild-type-like tagged allele of either the REC114 or MER2. The synthetic defect of the tagged REC114 allele in the DSB formation was seen also with the set1, but not with spp1 deletion. These results suggest a novel role of histone modification machinery in DSB formation during meiosis, which is independent of Spp1-mediated loop-axis tethering. Full article
(This article belongs to the Special Issue Mechanism of Chromosome Segregation in Eukaryotes)
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15 pages, 6246 KiB  
Article
Chromosome Missegregation in Single Human Oocytes Is Related to the Age and Gene Expression Profile
by Stefano Barone, Patrizia Sarogni, Roberto Valli, Maria Michela Pallotta, Gazzi Silvia, Annalisa Frattini, Abdul Waheed Khan, Erika Rapalini, Cristiana Parri and Antonio Musio
Int. J. Mol. Sci. 2020, 21(6), 1934; https://doi.org/10.3390/ijms21061934 - 12 Mar 2020
Cited by 12 | Viewed by 2920
Abstract
The growing trend for women to postpone childbearing has resulted in a dramatic increase in the incidence of aneuploid pregnancies. Despite the importance to human reproductive health, the events precipitating female age-related meiotic errors are poorly understood. To gain new insight into the [...] Read more.
The growing trend for women to postpone childbearing has resulted in a dramatic increase in the incidence of aneuploid pregnancies. Despite the importance to human reproductive health, the events precipitating female age-related meiotic errors are poorly understood. To gain new insight into the molecular basis of age-related chromosome missegregation in human oocytes, we combined the transcriptome profiles of twenty single oocytes (derived from females divided into two groups according to age <35 and ≥35 years) with their chromosome status obtained by array comparative genomic hybridization (aCGH). Furthermore, we compared the transcription profile of the single oocyte with the surrounding cumulus cells (CCs). RNA-seq data showed differences in gene expression between young and old oocytes. Dysregulated genes play a role in important biological processes such as gene transcription regulation, cytoskeleton organization, pathways related to RNA maturation and translation. The comparison of the transcription profile of the oocyte and the corresponding CCs highlighted the differential expression of genes belonging to the G protein-coupled receptor superfamily. Finally, we detected the loss of a X chromosome in two oocytes derived from women belonging to the ≥35 years age group. These aneuploidies may be caused by the detriment of REEP4, an endoplasmic reticulum protein, in women aged ≥35 years. Here we gained new insight into the complex regulatory circuit between the oocyte and the surrounding CCs and uncovered a new putative molecular basis of age-related chromosome missegregation in human oocytes. Full article
(This article belongs to the Special Issue Mechanism of Chromosome Segregation in Eukaryotes)
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18 pages, 3731 KiB  
Article
Two XMAP215/TOG Microtubule Polymerases, Alp14 and Dis1, Play Non-Exchangeable, Distinct Roles in Microtubule Organisation in Fission Yeast
by Masashi Yukawa, Tomoki Kawakami, Corinne Pinder and Takashi Toda
Int. J. Mol. Sci. 2019, 20(20), 5108; https://doi.org/10.3390/ijms20205108 - 15 Oct 2019
Cited by 4 | Viewed by 3262
Abstract
Proper bipolar spindle assembly underlies accurate chromosome segregation. A cohort of microtubule-associated proteins orchestrates spindle microtubule formation in a spatiotemporally coordinated manner. Among them, the conserved XMAP215/TOG family of microtubule polymerase plays a central role in spindle assembly. In fission yeast, two XMAP215/TOG [...] Read more.
Proper bipolar spindle assembly underlies accurate chromosome segregation. A cohort of microtubule-associated proteins orchestrates spindle microtubule formation in a spatiotemporally coordinated manner. Among them, the conserved XMAP215/TOG family of microtubule polymerase plays a central role in spindle assembly. In fission yeast, two XMAP215/TOG members, Alp14 and Dis1, share essential roles in cell viability; however how these two proteins functionally collaborate remains undetermined. Here we show the functional interplay and specification of Alp14 and Dis1. Creation of new mutant alleles of alp14, which display temperature sensitivity in the absence of Dis1, enabled us to conduct detailed analyses of a double mutant. We have found that simultaneous inactivation of Alp14 and Dis1 results in early mitotic arrest with very short, fragile spindles. Intriguingly, these cells often undergo spindle collapse, leading to a lethal “cut” phenotype. By implementing an artificial targeting system, we have shown that Alp14 and Dis1 are not functionally exchangeable and as such are not merely redundant paralogues. Interestingly, while Alp14 promotes microtubule nucleation, Dis1 does not. Our results uncover that the intrinsic specification, not the spatial regulation, between Alp14 and Dis1 underlies the collaborative actions of these two XMAP215/TOG members in mitotic progression, spindle integrity and genome stability. Full article
(This article belongs to the Special Issue Mechanism of Chromosome Segregation in Eukaryotes)
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Review

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14 pages, 1648 KiB  
Review
Shake It Off: The Elimination of Erroneous Kinetochore-Microtubule Attachments and Chromosome Oscillation
by Ayumu Yamamoto
Int. J. Mol. Sci. 2021, 22(6), 3174; https://doi.org/10.3390/ijms22063174 - 20 Mar 2021
Cited by 5 | Viewed by 4285
Abstract
Cell proliferation and sexual reproduction require the faithful segregation of chromosomes. Chromosome segregation is driven by the interaction of chromosomes with the spindle, and the attachment of chromosomes to the proper spindle poles is essential. Initial attachments are frequently erroneous due to the [...] Read more.
Cell proliferation and sexual reproduction require the faithful segregation of chromosomes. Chromosome segregation is driven by the interaction of chromosomes with the spindle, and the attachment of chromosomes to the proper spindle poles is essential. Initial attachments are frequently erroneous due to the random nature of the attachment process; however, erroneous attachments are selectively eliminated. Proper attachment generates greater tension at the kinetochore than erroneous attachments, and it is thought that attachment selection is dependent on this tension. However, studies of meiotic chromosome segregation suggest that attachment elimination cannot be solely attributed to tension, and the precise mechanism of selective elimination of erroneous attachments remains unclear. During attachment elimination, chromosomes oscillate between the spindle poles. A recent study on meiotic chromosome segregation in fission yeast has suggested that attachment elimination is coupled to chromosome oscillation. In this review, the possible contribution of chromosome oscillation in the elimination of erroneous attachment is discussed in light of the recent finding. Full article
(This article belongs to the Special Issue Mechanism of Chromosome Segregation in Eukaryotes)
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17 pages, 5298 KiB  
Review
Super-Resolution Microscopy Reveals Diversity of Plant Centromere Architecture
by Veit Schubert, Pavel Neumann, André Marques, Stefan Heckmann, Jiri Macas, Andrea Pedrosa-Harand, Ingo Schubert, Tae-Soo Jang and Andreas Houben
Int. J. Mol. Sci. 2020, 21(10), 3488; https://doi.org/10.3390/ijms21103488 - 15 May 2020
Cited by 31 | Viewed by 7110
Abstract
Centromeres are essential for proper chromosome segregation to the daughter cells during mitosis and meiosis. Chromosomes of most eukaryotes studied so far have regional centromeres that form primary constrictions on metaphase chromosomes. These monocentric chromosomes vary from point centromeres to so-called “meta-polycentromeres”, with [...] Read more.
Centromeres are essential for proper chromosome segregation to the daughter cells during mitosis and meiosis. Chromosomes of most eukaryotes studied so far have regional centromeres that form primary constrictions on metaphase chromosomes. These monocentric chromosomes vary from point centromeres to so-called “meta-polycentromeres”, with multiple centromere domains in an extended primary constriction, as identified in Pisum and Lathyrus species. However, in various animal and plant lineages centromeres are distributed along almost the entire chromosome length. Therefore, they are called holocentromeres. In holocentric plants, centromere-specific proteins, at which spindle fibers usually attach, are arranged contiguously (line-like), in clusters along the chromosomes or in bands. Here, we summarize findings of ultrastructural investigations using immunolabeling with centromere-specific antibodies and super-resolution microscopy to demonstrate the structural diversity of plant centromeres. A classification of the different centromere types has been suggested based on the distribution of spindle attachment sites. Based on these findings we discuss the possible evolution and advantages of holocentricity, and potential strategies to segregate holocentric chromosomes correctly. Full article
(This article belongs to the Special Issue Mechanism of Chromosome Segregation in Eukaryotes)
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