4,167 results match your criteria spindle checkpoint


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.

Authors:
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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Clonogenic Assays to Detect Cell Fate in Mitotic Catastrophe.

Methods Mol Biol 2021 ;2267:227-239

Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, Equipe 11 Labellisée par la Ligue Contre le Cancer, Paris, France.

Mitotic catastrophe (MC) is a cell death modality induced by DNA damage that involves the activation of cell cycle checkpoints such as the "DNA structure checkpoint" and "spindle assembly checkpoint" (SAC) leading to aberrant mitosis. Depending on the signal, MC can drive the cell to death or to senescence. The suppression of MC favors aneuploidy. Read More

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January 2021

Behavior of dicentric chromosomes in budding yeast.

PLoS Genet 2021 Mar 18;17(3):e1009442. Epub 2021 Mar 18.

Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.

DNA double-strand breaks arise in vivo when a dicentric chromosome (two centromeres on one chromosome) goes through mitosis with the two centromeres attached to opposite spindle pole bodies. Repair of the DSBs generates phenotypic diversity due to the range of monocentric derivative chromosomes that arise. To explore whether DSBs may be differentially repaired as a function of their spatial position in the chromosome, we have examined the structure of monocentric derivative chromosomes from cells containing a suite of dicentric chromosomes in which the distance between the two centromeres ranges from 6. Read More

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Identification of a novel Bax-Cdk1 signalling complex that links activation of the mitotic checkpoint to apoptosis.

J Cell Sci 2021 Mar 15. Epub 2021 Mar 15.

Department of Molecular and Cell Biology, University of Leicester, UK

In eucaryotes entry into and exit from mitosis is regulated, respectively, by the transient activation and inactivation of Cdk1. Taxol, an anti-microtubule anti-cancer drug, prevents microtubule-kinetochore attachments to induce Spindle Assembly Checkpoint (SAC, also known as the Mitotic Checkpoint)-activated mitotic arrest. SAC activation causes mitotic arrest by chronically activating Cdk1. Read More

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A missense variant in NUF2, a component of the kinetochore NDC80 complex, causes impaired chromosome segregation and aneuploidy associated with microcephaly and short stature.

Hum Genet 2021 Mar 15. Epub 2021 Mar 15.

Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

Mutations in proteins involved in cell division and chromosome segregation, such as microtubule-regulating, centrosomal and kinetochore proteins, are associated with microcephaly and/or short stature. In particular, the kinetochore plays an essential role in mitosis and cell division by mediating connections between chromosomal DNA and spindle microtubules. To date, only a few genes encoding proteins of the kinetochore complex have been identified as causes of syndromes that include microcephaly. Read More

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Bub1 kinase in the regulation of mitosis.

Anim Cells Syst (Seoul) 2021 Feb 17;25(1):1-10. Epub 2021 Feb 17.

IBS Center for Genomic Integrity, Ulsan, Korea.

Accurate chromosome segregation is required for cell survival and organismal development. During mitosis, the spindle assembly checkpoint acts as a safeguard to maintain the high fidelity of mitotic chromosome segregation by monitoring the attachment of kinetochores to the mitotic spindle. Bub1 is a conserved kinase critical for the spindle assembly checkpoint. Read More

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February 2021

[Expression and clinical significance of SETD2 in maligant pleural mesothelioma].

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2021 Feb;39(2):91-98

Hangzhou Medical School (Zhejiang Academy of Medical Sciences) , School of Public Health, Hangzhou 310013, China.

To analyze the gene mutation profile in malignant pleural mesothelioma (MPM) and investigate the expression of high-frequency mutant genes and its relationship with clinicopathological parameters. To screen out key genes and clinicopathologic factors related to the prognosis of MPM patients. The second generation sequencing data, somatic mutation data and clinical pathological data of 86 MPM cases and gene chip expression data of 89 MPM cases were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) in March 2020. Read More

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February 2021

TTK inhibitor promotes radiosensitivity of liver cancer cells through p21.

Biochem Biophys Res Commun 2021 Apr 6;550:84-91. Epub 2021 Mar 6.

Graduate Department, Bengbu Medical College, Bengbu, Anhui, 233000, PR China; Department of Radiation Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, PR China. Electronic address:

The monopolar spindle 1 ((hMps1/TTK) is a serine/threonine kinase that plays an important role in spindle assembly checkpoint signaling. To explore the possible relationship between TTK inhibition and radiosensitivity, we examined whether TTK inhibition influences cellular susceptibility of radiation. And we further revealed its mechanisms. Read More

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A case of multiple metastatic sarcomatoid renal cell carcinoma with complete response to nivolumab.

Cancer Rep (Hoboken) 2021 Mar 3:e1356. Epub 2021 Mar 3.

Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan.

Background: Sarcomatoid renal cell carcinoma (SRCC) is associated with poor prognosis. Although there is no standard treatment for SRCC, recent studies have reported the effectiveness of immune checkpoint inhibitors.

Case: An 82-year-old Japanese man presented to our hospital with an incidental right renal tumor. Read More

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Kinetochore stretching-mediated rapid silencing of the spindle-assembly checkpoint required for failsafe chromosome segregation.

Curr Biol 2021 Feb 22. Epub 2021 Feb 22.

Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan. Electronic address:

The spindle-assembly checkpoint facilitates mitotic fidelity by delaying anaphase onset in response to microtubule vacancy at kinetochores. Following microtubule attachment, kinetochores receive microtubule-derived force, which causes kinetochores to undergo repetitive cycles of deformation; this phenomenon is referred to as kinetochore stretching. The nature of the forces and the relevance relating this deformation are not well understood. Read More

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February 2021

Identification of Potential Therapeutic Genes and Pathways in Phytoestrogen Emodin Treated Breast Cancer Cell Lines via Network Biology Approaches.

Nutr Cancer 2021 Mar 1:1-13. Epub 2021 Mar 1.

Department of Biotechnology, Middle East Technical University, Ankara, Turkey.

Phytoestrogens have been investigated for their potential anti-tumorigenic effects in various cancers including breast cancer. Emodin being a phytoestrogen shows anti-carcinogenic properties especially in estrogen receptor positive (ER+) breast cancers. The aim of this study is to identify the molecular mechanism and related biological pathways in both (ER+) MCF-7 and (ER-) MDA-MB-231 breast cancer cell lines upon Emodin treatment via microarray analysis in order to find out therapeutic biomarkers. Read More

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High Dosages of Equine Chorionic Gonadotropin Exert Adverse Effects on the Developmental Competence of IVF-Derived Mouse Embryos and Cause Oxidative Stress-Induced Aneuploidy.

Front Cell Dev Biol 2020 9;8:609290. Epub 2021 Feb 9.

Department of Reproductive Center, The First Affiliated Hospital of Shantou University Medical College, Shantou University, Shantou, China.

Gonadotropins play vital roles in the regulation of female reproductive ability and fertility. Our study aimed to determine the effects of superovulation induced by increasing doses of equine chorionic gonadotropin [eCG; also referred to as pregnant mare serum gonadotropin (PMSG)] on the developmental competence of mouse embryos and on aneuploidy formation during fertilization (IVF). eCG dose-dependently enhanced the oocyte yield from each mouse. Read More

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February 2021

Single-cell analysis of erythropoiesis in Rpl11 haploinsufficient mice reveals insight into the pathogenesis of Diamond-Blackfan anemia.

Exp Hematol 2021 Feb 22. Epub 2021 Feb 22.

Department of Medicine, Division of Hematology, University of Washington, Seattle, WA.

Rpl11 haploinsufficient mice develop a macrocytic anemia similar to patients with DBA. Here, we fully characterize this model from clinical and pathophysiological perspectives. Early erythroid precursors have increased heme content and high cytoplasmic reactive oxygen species, impairing erythroid differentiation at the colony-forming unit-erythroid (CFU-E)/proerythroblast stage and subsequently. Read More

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February 2021

Chromosomally unstable tumor cells specifically require KIF18A for proliferation.

Nat Commun 2021 02 22;12(1):1213. Epub 2021 Feb 22.

Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT, USA.

Chromosomal instability (CIN) is a hallmark of tumor cells caused by changes in the dynamics and control of microtubules that compromise the mitotic spindle. Thus, CIN cells may respond differently than diploid cells to treatments that target mitotic spindle regulation. Here, we test this idea by inhibiting a subset of kinesin motor proteins involved in mitotic spindle control. Read More

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February 2021

Transcriptomic analysis of nonylphenol effect on .

PeerJ 2021 11;9:e10794. Epub 2021 Feb 11.

Biology, The Life Science Center, School of Science and Technology, Örebro University, Örebro, Sweden.

Nonylphenol (NP) is a bioaccumulative environmental estrogen that is widely used as a nonionic surfactant. We have previously examined short-term effects of NP on yeast cells using microarray technology. In the present study, we investigated the adaptive response of BY4742 cells to NP exposure by analyzing genome-wide transcriptional profiles using RNA-sequencing. Read More

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February 2021

Antagonizing the spindle assembly checkpoint silencing enhances paclitaxel and Navitoclax-mediated apoptosis with distinct mechanistic.

Sci Rep 2021 Feb 18;11(1):4139. Epub 2021 Feb 18.

CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde, Rua Central da Gandra 1317, Gandra, 4585-116, Paredes, Portugal.

Antimitotic drugs arrest cells in mitosis through chronic activation of the spindle assembly checkpoint (SAC), leading to cell death. However, drug-treated cancer cells can escape death by undergoing mitotic slippage, due to premature mitotic exit. Therefore, overcoming slippage issue is a promising chemotherapeutic strategy to improve the effectiveness of antimitotics. Read More

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February 2021

BUB1B Overexpression Is an Independent Prognostic Marker and Associated with CD44, p53, and PD-L1 in Renal Cell Carcinoma.

Oncology 2021 15;99(4):240-250. Epub 2021 Feb 15.

Department of Urology, Hiroshima General Hospital, Hatsukaichi, Japan.

Introduction: BUB1 mitotic checkpoint serine/threonine kinase B encoded by BUB1B gene is a member of the spindle assembly checkpoint family. Several reports have demonstrated that overexpression of BUB1B is associated with cancer progression and prognosis.

Objective: This study aims to clarify the expression and function of BUB1B in renal cell carcinoma (RCC). Read More

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February 2021

Spindle Architectural Features Must Be Considered Along With Cell Size to Explain the Timing of Mitotic Checkpoint Silencing.

Front Physiol 2020 28;11:596263. Epub 2021 Jan 28.

Department of Biological Sciences and Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA, United States.

Mitosis proceeds through a defined series of events that is largely conserved, but the amount of time needed for their completion can vary in different cells and organisms. In many systems, mitotic duration depends on the time required to satisfy and silence the spindle assembly checkpoint (SAC), also known as the mitotic checkpoint. Because SAC silencing involves trafficking SAC molecules among kinetochores, spindle, and cytoplasm, the size and geometry of the spindle relative to cell volume are expected to affect mitotic duration by influencing the timing of SAC silencing. Read More

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January 2021

Dual Inhibition of γ-Tubulin and Plk1 Induces Mitotic Cell Death.

Front Pharmacol 2020 29;11:620185. Epub 2021 Jan 29.

Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.

α/β-Tubulin inhibitors that alter microtubule (MT) dynamics are commonly used in cancer therapy, however, these inhibitors also cause severe side effects such as peripheral neuropathy. γ-Tubulin is a possible target as antitumor drugs with low side effects, but the antitumor effect of γ-tubulin inhibitors has not been reported yet. In this study, we verified the antitumor activity of gatastatin, a γ-tubulin specific inhibitor. Read More

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January 2021

The long noncoding RNA CRYBG3 induces aneuploidy by interfering with spindle assembly checkpoint via direct binding with Bub3.

Oncogene 2021 Mar 9;40(10):1821-1835. Epub 2021 Feb 9.

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Institute of Space Life Sciences, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China.

Aneuploidy is a hallmark of genomic instability that leads to tumor initiation, progression, and metastasis. CDC20, Bub1, and Bub3 form the mitosis checkpoint complex (MCC) that binds the anaphase-promoting complex or cyclosome (APC/C), a crucial factor of the spindle assembly checkpoint (SAC), to ensure the bi-directional attachment and proper segregation of all sister chromosomes. However, just how MCC is regulated to ensure normal mitosis during cellular division remains unclear. Read More

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Fbf1 regulates mouse oocyte meiosis by influencing Plk1.

Theriogenology 2021 Apr 29;164:74-83. Epub 2021 Jan 29.

Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China. Electronic address:

Fas binding factor 1 (Fbf1) is one of the distal appendage proteins in the centriole, located at its distal and proximal ends. It influences the duplication and separation of centrosomes, thereby affecting the progression of the cell cycle during mitosis. However, the function of Fbf1 in meiosis has remained unclear. Read More

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Drosophila female germline stem cells undergo mitosis without nuclear breakdown.

Curr Biol 2021 Feb 1. Epub 2021 Feb 1.

Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA. Electronic address:

Stem cell homeostasis requires nuclear lamina (NL) integrity. In Drosophila germ cells, compromised NL integrity activates the ataxia telangiectasia and Rad3-related (ATR) and checkpoint kinase 2 (Chk2) checkpoint kinases, blocking germ cell differentiation and causing germline stem cell (GSC) loss. Checkpoint activation occurs upon loss of either the NL protein emerin or its partner barrier-to-autointegration factor, two proteins required for nuclear reassembly at the end of mitosis. Read More

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February 2021

The Spindle Assembly Checkpoint Is a Vulnerability of Aneuploid Cells.

Authors:

Cancer Discov 2021 Mar 5;11(3):533. Epub 2021 Feb 5.

Cancer cells with abnormal chromosome numbers were sensitive to spindle assembly checkpoint inhibition. Read More

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A New Method for Chromosomes Preparation by ATP-Competitive Inhibitor SP600125 Enhancement of Endomitosis in Fish.

Front Bioeng Biotechnol 2020 13;8:606496. Epub 2021 Jan 13.

State Key Laboratory of Developmental Biology of Freshwater Fish, Hunan Normal University, Changsha, China.

Previous studies have suggested that 1,9-Pyrazoloanthrone, known as SP600125, can induce cell polyploidization. However, what is the phase of cell cycle arrest caused by SP600125 and the underlying regulation is still an interesting issue to be further addressed. Research in this article shows that SP600125 can block cell cycle progression at the prometaphase of mitosis and cause endomitosis. Read More

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January 2021

Kinetochore-independent mechanisms of sister chromosome separation.

PLoS Genet 2021 Jan 29;17(1):e1009304. Epub 2021 Jan 29.

Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California, United States of America.

Although kinetochores normally play a key role in sister chromatid separation and segregation, chromosome fragments lacking kinetochores (acentrics) can in some cases separate and segregate successfully. In Drosophila neuroblasts, acentric chromosomes undergo delayed, but otherwise normal sister separation, revealing the existence of kinetochore- independent mechanisms driving sister chromosome separation. Bulk cohesin removal from the acentric is not delayed, suggesting factors other than cohesin are responsible for the delay in acentric sister separation. Read More

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January 2021

The Mad2-Binding Protein p31comet as a potential target for human cancer therapy.

Curr Cancer Drug Targets 2021 Jan 28. Epub 2021 Jan 28.

Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde, CESPU, Gandra. Portugal.

The spindle assembly checkpoint (SAC) is a surveillance mechanism that prevents mitotic exit at the metaphase-to-anaphase transition until all chromosomes have established correct bipolar attachment to spindle microtubules. Activation of SAC relies on the assembly of the mitotic checkpoint complex (MCC), which requires conformational change from inactive open Mad2 (O-Mad2) to the active closed Mad2 (C-Mad2) at unattached kinetochores. The Mad2-binding protein p31comet plays a key role in controlling timely mitotic exit by promoting SAC silencing, through preventing Mad2 activation and promoting MCC disassembly. Read More

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January 2021

Aneuploidy renders cancer cells vulnerable to mitotic checkpoint inhibition.

Nature 2021 02 27;590(7846):486-491. Epub 2021 Jan 27.

Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Selective targeting of aneuploid cells is an attractive strategy for cancer treatment. However, it is unclear whether aneuploidy generates any clinically relevant vulnerabilities in cancer cells. Here we mapped the aneuploidy landscapes of about 1,000 human cancer cell lines, and analysed genetic and chemical perturbation screens to identify cellular vulnerabilities associated with aneuploidy. Read More

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February 2021

Whole-genome doubling confers unique genetic vulnerabilities on tumour cells.

Nature 2021 02 27;590(7846):492-497. Epub 2021 Jan 27.

Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.

Whole-genome doubling (WGD) is common in human cancers, occurring early in tumorigenesis and generating genetically unstable tetraploid cells that fuel tumour development. Cells that undergo WGD (WGD cells) must adapt to accommodate their abnormal tetraploid state; however, the nature of these adaptations, and whether they confer vulnerabilities that can be exploited therapeutically, is unclear. Here, using sequencing data from roughly 10,000 primary human cancer samples and essentiality data from approximately 600 cancer cell lines, we show that WGD gives rise to common genetic traits that are accompanied by unique vulnerabilities. Read More

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February 2021