3,747 results match your criteria anaphase spindle

Three-dimensional geometry controls division symmetry in stem cell colonies.

J Cell Sci 2021 Jun 23. Epub 2021 Jun 23.

MRC Laboratory for Molecular Cell Biology, University College London, London, UK.

Proper control of division orientation and symmetry, largely determined by spindle positioning, is essential to development and homeostasis. Spindle positioning has been extensively studied in cells dividing in 2-dimensional (2D) environments and in epithelial tissues, where proteins such as NuMA orient division along the cell's interphase long axis. However, little is known about how cells control spindle positioning in 3-dimensional (3D) environments, such as early mammalian embryos and a variety of adult tissues. Read More

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WDR62 localizes katanin at spindle poles to ensure synchronous chromosome segregation.

J Cell Biol 2021 Aug 17;220(8). Epub 2021 Jun 17.

Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Mutations in the WDR62 gene cause primary microcephaly, a pathological condition often associated with defective cell division that results in severe brain developmental defects. The precise function and localization of WDR62 within the mitotic spindle is, however, still under debate, as it has been proposed to act either at centrosomes or on the mitotic spindle. Here we explored the cellular functions of WDR62 in human epithelial cell lines using both short-term siRNA protein depletions and long-term CRISPR/Cas9 gene knockouts. Read More

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Semin Cell Dev Biol 2021 Jun 11. Epub 2021 Jun 11.

Chromosome Instability & Dynamics Group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Cell Division Group, Experimental Biology Unit, Department of Biomedicine, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address:

The establishment of a metaphase plate in which all chromosomes are attached to mitotic spindle microtubules and aligned at the cell equator is required for faithful chromosome segregation in metazoans. The achievement of this configuration relies on the precise coordination between several concurrent mechanisms that start upon nuclear envelope breakdown, mediate chromosome capture at their kinetochores during mitotic spindle assembly and culminate with the congression of all chromosomes to the spindle equator. This period is called 'prometaphase'. Read More

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Microtubule reorganization during female meiosis in .

Elife 2021 Jun 11;10. Epub 2021 Jun 11.

Center for Membrane and Cell Physiology, University of Virginia School of Medicine, Charlottesville, United States.

Most female meiotic spindles undergo striking morphological changes while transitioning from metaphase to anaphase. The ultra-structure of meiotic spindles, and how changes to this structure correlate with such dramatic spindle rearrangements remains largely unknown. To address this, we applied light microscopy, large-scale electron tomography and mathematical modeling of female meiotic spindles. Read More

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Mapping Proximity Associations of Core Spindle Assembly Checkpoint Proteins.

J Proteome Res 2021 Jun 4. Epub 2021 Jun 4.

Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.

The spindle assembly checkpoint (SAC) is critical for sensing defective microtubule-kinetochore attachments and tension across the kinetochore and functions to arrest cells in prometaphase to allow time to repair any errors before proceeding into anaphase. Dysregulation of the SAC leads to chromosome segregation errors that have been linked to human diseases like cancer. Although much has been learned about the composition of the SAC and the factors that regulate its activity, the proximity associations of core SAC components have not been explored in a systematic manner. Read More

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Differential regulation of single microtubules and bundles by a three-protein module.

Nat Chem Biol 2021 Jun 3. Epub 2021 Jun 3.

Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.

A remarkable feature of the microtubule cytoskeleton is the coexistence of subpopulations having different dynamic properties. A prominent example is the anaphase spindle, where stable antiparallel bundles exist alongside dynamic microtubules and provide spatial cues for cytokinesis. How are the dynamics of spatially proximal arrays differentially regulated? We reconstitute a minimal system of three midzone proteins: microtubule-crosslinker PRC1 and its interactors CLASP1 and Kif4A, proteins that promote and suppress microtubule elongation, respectively. Read More

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Ctf3/CENP-I provides a docking site for the desumoylase Ulp2 at the kinetochore.

J Cell Biol 2021 Aug 3;220(8). Epub 2021 Jun 3.

Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA.

The step-by-step process of chromosome segregation defines the stages of the cell cycle. In eukaryotes, signals controlling these steps converge upon the kinetochore, a multiprotein assembly that connects spindle microtubules to chromosomal centromeres. Kinetochores control and adapt to major chromosomal transactions, including replication of centromeric DNA, biorientation of sister centromeres on the metaphase spindle, and transit of sister chromatids into daughter cells during anaphase. Read More

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CK1-mediated phosphorylation of FAM110A promotes its interaction with mitotic spindle and controls chromosomal alignment.

EMBO Rep 2021 May 26:e51847. Epub 2021 May 26.

Cancer Cell Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.

Progression through the cell cycle is driven by cyclin-dependent kinases that control gene expression, orchestration of mitotic spindle, and cell division. To identify new regulators of the cell cycle, we performed transcriptomic analysis of human non-transformed cells expressing a fluorescent ubiquitination-based cell cycle indicator and identified 701 transcripts differentially expressed in G1 and G2 cells. Family with sequence similarity 110 member A (FAM110A) protein is highly expressed in G2 cells and localized at mitotic spindle and spindle poles during mitosis. Read More

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Kinesin-6 Klp9 orchestrates spindle elongation by regulating microtubule sliding and growth.

Elife 2021 Jun 3;10. Epub 2021 Jun 3.

Institut Curie, PSL Research University, Sorbonne Université CNRS, UMR 144, Paris, France.

Mitotic spindle function depends on the precise regulation of microtubule dynamics and microtubule sliding. Throughout mitosis, both processes have to be orchestrated to establish and maintain spindle stability. We show that during anaphase B spindle elongation in , the sliding motor Klp9 (kinesin-6) also promotes microtubule growth in vivo. Read More

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The metaphase spindle at steady state - Mechanism and functions of microtubule poleward flux.

Semin Cell Dev Biol 2021 May 27. Epub 2021 May 27.

Cell Division and Cytoskeleton, Danish Cancer Society Research Center (DCRC), Strandboulevarden 49, 2100 Copenhagen, Denmark.

The mitotic spindle is a bipolar cellular structure, built from tubulin polymers, called microtubules, and interacting proteins. This macromolecular machine orchestrates chromosome segregation, thereby ensuring accurate distribution of genetic material into the two daughter cells during cell division. Powered by GTP hydrolysis upon tubulin polymerization, the microtubule ends exhibit a metastable behavior known as the dynamic instability, during which they stochastically switch between the growth and shrinkage phases. Read More

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Energy restriction causes metaphase delay and chromosome mis-segregation in cancer cells.

Cell Cycle 2021 May 28:1-14. Epub 2021 May 28.

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

ATP metabolism during mitosis needs to be coordinated with numerous energy-demanding activities, especially in cancer cells whose metabolic pathways are reprogramed to sustain rapid proliferation in a nutrient-deficient environment. Although strategies targeting the energy metabolic pathways have shown therapeutic efficacy in preclinical cancer models, how normal cells and cancer cells differentially respond to energy shortage is unclear. In this study, using time-lapse microscopy, we found that cancer cells displayed unique mitotic phenotypes in a dose-dependent manner upon decreasing ATP (i. Read More

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The multifunctional spindle midzone in vertebrate cells at a glance.

J Cell Sci 2021 May 27;134(10). Epub 2021 May 27.

Department of Biology, Morrill Science Center, University of Massachusetts, 611 N. Pleasant Street, Amherst 01003, USA.

During anaphase, a microtubule-containing structure called the midzone forms between the segregating chromosomes. The midzone is composed of an antiparallel array of microtubules and numerous microtubule-associated proteins that contribute to midzone formation and function. In many cells, the midzone is an important source of signals that specify the location of contractile ring assembly and constriction. Read More

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Biomechanics of chromosome alignment at the spindle midplane.

Curr Biol 2021 May;31(10):R574-R585

Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia. Electronic address:

During metaphase, chromosomes are aligned in a lineup at the equatorial plane of the spindle to ensure synchronous poleward movement of chromatids in anaphase and proper nuclear reformation at the end of mitosis. Chromosome alignment relies on microtubules, several types of motor protein and numerous other microtubule-associated and regulatory proteins. Because of the multitude of players involved, the mechanisms of chromosome alignment are still under debate. Read More

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Yeast Fin1-PP1 dephosphorylates an Ipl1 substrate, Ndc80, to remove Bub1-Bub3 checkpoint proteins from the kinetochore during anaphase.

PLoS Genet 2021 May 25;17(5):e1009592. Epub 2021 May 25.

Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, United States of America.

The spindle assembly checkpoint (SAC) prevents anaphase onset in response to chromosome attachment defects, and SAC silencing is essential for anaphase onset. Following anaphase onset, activated Cdc14 phosphatase dephosphorylates the substrates of cyclin-dependent kinase to facilitate anaphase progression and mitotic exit. In budding yeast, Cdc14 dephosphorylates Fin1, a regulatory subunit of protein phosphatase 1 (PP1), to enable kinetochore localization of Fin1-PP1. Read More

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Unraveling pathologies underlying chromosomal instability in cancers.

Cancer Sci 2021 May 25. Epub 2021 May 25.

Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan.

Aneuploidy is a widespread feature of malignant tumors that arises through persistent chromosome mis-segregation in mitosis associated with a pathological condition called chromosomal instability, or CIN. Since CIN is known to have a causal relationship with poor prognosis accompanying by multi-drug resistance, tumor relapse, and metastasis, many research groups have endeavored to understand the mechanisms underlying CIN. In this review, we overview possible etiologies of CIN. Read More

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Molecular mechanism of Mad1 kinetochore targeting by phosphorylated Bub1.

EMBO Rep 2021 May 19:e52242. Epub 2021 May 19.

MRC Laboratory of Molecular Biology, Cambridge, UK.

During metaphase, in response to improper kinetochore-microtubule attachments, the spindle assembly checkpoint (SAC) activates the mitotic checkpoint complex (MCC), an inhibitor of the anaphase-promoting complex/cyclosome (APC/C). This process is orchestrated by the kinase Mps1, which initiates the assembly of the MCC onto kinetochores through a sequential phosphorylation-dependent signalling cascade. The Mad1-Mad2 complex, which is required to catalyse MCC formation, is targeted to kinetochores through a direct interaction with the phosphorylated conserved domain 1 (CD1) of Bub1. Read More

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A Hypomorphic Mutant of PHD Domain Protein Male Meiocytes Death 1.

Genes (Basel) 2021 Apr 1;12(4). Epub 2021 Apr 1.

Unit HortiCell, Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium.

Meiosis drives reciprocal genetic exchanges and produces gametes with halved chromosome number, which is important for the genetic diversity, plant viability, and ploidy consistency of flowering plants. Alterations in chromosome dynamics and/or cytokinesis during meiosis may lead to meiotic restitution and the formation of unreduced microspores. In this study, we isolated an mutant (), which produces a small subpopulation of diploid or polyploid pollen grains. Read More

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Microtubule-sliding modules based on kinesins EG5 and PRC1-dependent KIF4A drive human spindle elongation.

Dev Cell 2021 May 27;56(9):1253-1267.e10. Epub 2021 Apr 27.

Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia. Electronic address:

Proper chromosome segregation into two future daughter cells requires the mitotic spindle to elongate in anaphase. However, although some candidate proteins are implicated in this process, the molecular mechanism that drives spindle elongation in human cells is unknown. Using combined depletion and inactivation assays together with CRISPR technology to explore redundancy between multiple targets, we discovered that the force-generating mechanism of spindle elongation consists of EG5/kinesin-5 together with the PRC1-dependent motor KIF4A/kinesin-4, with contribution from kinesin-6 and kinesin-8. Read More

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The coordination of spindle-positioning forces during the asymmetric division of the Caenorhabditis elegans zygote.

EMBO Rep 2021 05 26;22(5):e50770. Epub 2021 Apr 26.

CNRS, IGDR - UMR 6290, University of Rennes, Rennes, France.

In Caenorhabditis elegans zygote, astral microtubules generate forces essential to position the mitotic spindle, by pushing against and pulling from the cortex. Measuring microtubule dynamics there, we revealed the presence of two populations, corresponding to pulling and pushing events. It offers a unique opportunity to study, under physiological conditions, the variations of both spindle-positioning forces along space and time. Read More

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Inhibition of polar actin assembly by astral microtubules is required for cytokinesis.

Nat Commun 2021 04 23;12(1):2409. Epub 2021 Apr 23.

Department of Biochemistry, University of Toronto, Toronto, ON, Canada.

During cytokinesis, the actin cytoskeleton is partitioned into two spatially distinct actin isoform specific networks: a β-actin network that generates the equatorial contractile ring, and a γ-actin network that localizes to the cell cortex. Here we demonstrate that the opposing regulation of the β- and γ-actin networks is required for successful cytokinesis. While activation of the formin DIAPH3 at the cytokinetic furrow underlies β-actin filament production, we show that the γ-actin network is specifically depleted at the cell poles through the localized deactivation of the formin DIAPH1. Read More

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Physiological relevance of post-translational regulation of the spindle assembly checkpoint protein BubR1.

Cell Biosci 2021 Apr 23;11(1):76. Epub 2021 Apr 23.

Biomedical Sciences Department, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE, 68178, USA.

BubR1 is an essential component of the spindle assembly checkpoint (SAC) during mitosis where it functions to prevent anaphase onset to ensure proper chromosome alignment and kinetochore-microtubule attachment. Loss or mutation of BubR1 results in aneuploidy that precedes various potential pathologies, including cancer and mosaic variegated aneuploidy (MVA). BubR1 is also progressively downregulated with age and has been shown to be directly involved in the aging process through suppression of cellular senescence. Read More

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WAPL orchestrates porcine oocyte meiotic progression via control of spindle assembly checkpoint activity.

Reprod Biol Endocrinol 2021 Apr 19;19(1):57. Epub 2021 Apr 19.

College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, China.

Background: In mitotic cells, WAPL acts as a cohesin release factor to remove cohesin complexes from chromosome arms during prophase to allow the accurate chromosome segregation in anaphase. However, we have recently documented that Wapl exerts a unique meiotic function in the spindle assembly checkpoint (SAC) control through maintaining Bub3 stability during mouse oocyte meiosis I. Whether this noncanonical function is conserved among species is still unknown. Read More

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Adventures of the undead at kinetochores.

Sabine Elowe

Mol Cell Oncol 2021 31;8(2):1876511. Epub 2021 Jan 31.

Axe de reproduction, santé de la mère et de l'enfant, Centre de recherche du Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec, QC, Canada.

At the metaphase-to-anaphase transition, phosphatase activity feeds back to reverse early mitotic phosphorylation events. Our recent work indicates that the pseudokinase domain of the spindle checkpoint protein BUB1 (Budding Uninhibited by Benzimidazoles 1) mitotic checkpoint serine/threonine kinase B (BUB1B, BUBR1) maintains kinase-phosphatase balance at the outer kinetochore during mitotic exit. Read More

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January 2021

Anaphase B: Long-standing models meet new concepts.

Semin Cell Dev Biol 2021 Apr 10. Epub 2021 Apr 10.

Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia. Electronic address:

Mitotic cell divisions ensure stable transmission of genetic information from a mother to daughter cells in a series of generations. To ensure this crucial task is accomplished, the cell forms a bipolar structure called the mitotic spindle that divides sister chromatids to the opposite sides of the dividing mother cell. After successful establishment of stable attachments of microtubules to chromosomes and inspection of connections between them, at the heart of mitosis, the cell starts the process of segregation. Read More

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FBXO34 Regulates the G2/M Transition and Anaphase Entry in Meiotic Oocytes.

Front Cell Dev Biol 2021 25;9:647103. Epub 2021 Mar 25.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

There are two important events in oocyte meiotic maturation, the G2/M transition and metaphase I progression. Thousands of proteins participate in regulating oocyte maturation, which highlights the importance of the ubiquitin proteasome system (UPS) in regulating protein synthesis and degradation. Skp1-Cullin-F-box (SCF) complexes, as the best characterized ubiquitin E3 ligases in the UPS, specifically recognize their substrates. Read More

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Coupling of Cdc20 inhibition and activation by BubR1.

J Cell Biol 2021 May;220(5)

Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Science, Copenhagen, Denmark.

Tight regulation of the APC/C-Cdc20 ubiquitin ligase that targets cyclin B1 for degradation is important for mitotic fidelity. The spindle assembly checkpoint (SAC) inhibits Cdc20 through the mitotic checkpoint complex (MCC). In addition, phosphorylation of Cdc20 by cyclin B1-Cdk1 independently inhibits APC/C-Cdc20 activation. Read More

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Back to the new beginning: Mitotic exit in space and time.

Paola Vagnarelli

Semin Cell Dev Biol 2021 Mar 30. Epub 2021 Mar 30.

College of Medicine, Health and Life Science, Centre for Genomic Engineering and Maintenance (CenGEM), Brunel University London, Uxbridge UB8 3PH, UK. Electronic address:

The ultimate goal of cell division is to generate two identical daughter cells that resemble the mother cell from which they derived. Once all the proper attachments to the spindle have occurred, the chromosomes have aligned at the metaphase plate and the spindle assembly checkpoint (a surveillance mechanism that halts cells form progressing in the cell cycle in case of spindle - microtubule attachment errors) has been satisfied, mitotic exit will occur. Mitotic exit has the purpose of completing the separation of the genomic material but also to rebuild the cellular structures necessary for the new cell cycle. Read More

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Molecular mechanisms of APC/C release from spindle assembly checkpoint inhibition by APC/C SUMOylation.

Cell Rep 2021 Mar;34(13):108929

MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address:

The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls cell cycle transitions. Its regulation by the spindle assembly checkpoint (SAC) is coordinated with the attachment of sister chromatids to the mitotic spindle. APC/C SUMOylation on APC4 ensures timely anaphase onset and chromosome segregation. Read More

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Hyaluronan-Mediated Motility Receptor Governs Chromosome Segregation by Regulating Microtubules Sliding Within the Bridging Fiber.

Adv Biol (Weinh) 2021 06 31;5(6):e2000493. Epub 2021 Mar 31.

Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore.

Accurate segregation of chromosomes during anaphase relies on the central spindle and its regulators. A newly raised concept of the central spindle, the bridging fiber, shows that sliding of antiparallel microtubules (MTs) within the bridging fiber promotes chromosome segregation. However, the regulators of the bridging fiber and its regulatory mechanism on MTs sliding remain largely unknown. Read More

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Seminars in cell and developmental biology: Anaphase A.

Semin Cell Dev Biol 2021 Mar 26. Epub 2021 Mar 26.

Dept. of Molecular, Cellular, and Developmental Biology University of Colorado, Boulder, CO 80309-0347, USA. Electronic address:

Anaphase A is the motion of recently separated chromosomes to the spindle pole they face. It is accompanied by the shortening of kinetochore-attached microtubules. The requisite tubulin depolymerization may occur at kinetochores, at poles, or both, depending on the species and/or the time in mitosis. Read More

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