651 results match your criteria fidelity segregation

Reduced Expression Impairs Mitotic Removal of H2B Monoubiquitination, Alters Chromatin Compaction and Induces Chromosome Instability That May Promote Oncogenesis.

Cancers (Basel) 2021 Mar 2;13(5). Epub 2021 Mar 2.

Research Institute in Oncology & Hematology, CancerCare Manitoba, Winnipeg, MB R3E0V9, Canada.

Chromosome instability (CIN) is an enabling feature of oncogenesis associated with poor patient outcomes, whose genetic determinants remain largely unknown. As mitotic chromatin compaction defects can compromise the accuracy of chromosome segregation into daughter cells and drive CIN, characterizing the molecular mechanisms ensuring accurate chromatin compaction may identify novel CIN genes. In vitro, histone H2B monoubiquitination at lysine 120 (H2Bub1) impairs chromatin compaction, while in vivo H2Bub1 is rapidly depleted from chromatin upon entry into mitosis, suggesting that H2Bub1 removal may be a pre-requisite for mitotic fidelity. Read More

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Novelty and convergence in adaptation to whole genome duplication.

Mol Biol Evol 2021 Mar 30. Epub 2021 Mar 30.

Future Food Beacon of Excellence, University of Nottingham, Nottingham, UK.

Whole genome duplication (WGD) can promote adaptation but is disruptive to conserved processes, especially meiosis. Studies in Arabidopsis arenosa revealed a coordinated evolutionary response to WGD involving interacting proteins controlling meiotic crossovers, which are minimised in an autotetraploid (within-species polyploid) to avoid mis-segregation. Here we test whether this surprising flexibility of a conserved essential process, meiosis, is recapitulated in an independent WGD system, Cardamine amara, 17 million years diverged from A. Read More

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Kinetochore assembly throughout the cell cycle.

Semin Cell Dev Biol 2021 Mar 19. Epub 2021 Mar 19.

Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address:

The kinetochore plays an essential role in facilitating chromosome segregation during cell division. This massive protein complex assembles onto the centromere of chromosomes and enables their attachment to spindle microtubules during mitosis. The kinetochore also functions as a signaling hub to regulate cell cycle progression, and is crucial to ensuring the fidelity of chromosome segregation. Read More

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From the cytoskeleton to the nucleus: An integrated view on early spindle assembly.

Semin Cell Dev Biol 2021 Mar 14. Epub 2021 Mar 14.

Instituto de Investigação e Inovação em Saúde - i3S, University of Porto, Porto, Portugal; Departamento de Biomedicina, Faculdade de Medicina, University of Porto, Porto, Portugal. Electronic address:

Accurate chromosome segregation requires a complete restructuring of cellular organization. Microtubules remodel to assemble a mitotic spindle and the actin cytoskeleton rearranges to form a stiff actomyosin cortex. These cytoplasmic events must be spatially and temporally coordinated with mitotic chromosome condensation and nuclear envelope permeabilization, in order to ensure mitotic timing and fidelity. Read More

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A case of convergent-gene interference in the budding yeast knockout library causing chromosome instability.

G3 (Bethesda) 2021 Mar 16. Epub 2021 Mar 16.

Department of Cell Biology, Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

To maintain genome stability, organisms depend on faithful chromosome segregation, a process affected by diverse genetic pathways, some of which are not directly linked to mitosis. In this study, we set out to explore one such pathway represented by an under-characterized gene, SNO1, identified previously in screens of the Yeast Knockout (YKO) library for mitotic fidelity genes. We found that the causative factor increasing mitotic error rate in the sno1Δ mutant is not loss of the Sno1 protein, but rather perturbation to the mRNA of the neighboring convergent gene, CTF13, encoding an essential component for forming the yeast kinetochore. 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

Challenges faced by highly polyploid bacteria with limits on DNA inheritance.

Esther R Angert

Genome Biol Evol 2021 Mar 2. Epub 2021 Mar 2.

Department of Microbiology, Cornell University, Wing Hall, Ithaca, NY, USA.

Most studies of bacterial reproduction have centered on organisms that undergo binary fission. In these models, complete chromosome copies are segregated with great fidelity into two equivalent offspring cells. All genetic material is passed on to offspring, including new mutations and horizontally acquired sequences. 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

Extract of bulbus of Fritillaria cirrhosa induces spindle multipolarity in human-derived colonic epithelial NCM460 cells through promoting centrosome fragmentation.

Mutagenesis 2021 Jan 15. Epub 2021 Jan 15.

School of Life Sciences, The Engineering Research Center of Sustainable Development and Utilization of Biomass Energy, Yunnan Normal University, Kunming, Yunnan, China.

Bulbus of Fritillaria cirrhosa D. Don (BFC), an outstanding antitussive and expectorant herbal drug used in China and many other countries, has potential but less understood genotoxicity. Previously, we have reported that aqueous extract of BFC compromised the spindle assembly checkpoint and cytokinesis in NCM460 cells. Read More

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January 2021

Fission Yeast Methylenetetrahydrofolate Reductase Ensures Mitotic and Meiotic Chromosome Segregation Fidelity.

Int J Mol Sci 2021 Jan 11;22(2). Epub 2021 Jan 11.

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.

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 , which encodes a protein that is highly homologous to the mammalian MTHFR. Read More

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January 2021

Hit the brakes - a new perspective on the loop extrusion mechanism of cohesin and other SMC complexes.

J Cell Sci 2021 Jan 8;134(1). Epub 2021 Jan 8.

8 Henrietta Szold St., The Azrieli Faculty of Medicine, Bar-Ilan University, P.O. Box 1589 Safed, Israel

The three-dimensional structure of chromatin is determined by the action of protein complexes of the structural maintenance of chromosome (SMC) family. Eukaryotic cells contain three SMC complexes, cohesin, condensin, and a complex of Smc5 and Smc6. Initially, cohesin was linked to sister chromatid cohesion, the process that ensures the fidelity of chromosome segregation in mitosis. Read More

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January 2021

A Mitochondrial Orthologue of the dNTP Triphosphohydrolase SAMHD1 Is Essential and Controls Pyrimidine Homeostasis in .

ACS Infect Dis 2021 02 8;7(2):318-332. Epub 2021 Jan 8.

Instituto de Parasitología y Biomedicina "López-Neyra", Consejo Superior de Investigaciones Científicas, Parque Tecnológico de Ciencias de la Salud, Armilla (Granada) 18016, Spain.

The maintenance of deoxyribonucleotide triphosphate (dNTP) homeostasis through synthesis and degradation is critical for accurate genomic and mitochondrial DNA replication fidelity. makes use of both the salvage and pathways for the provision of pyrimidine dNTPs. In this respect, the sterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) appears to be the most relevant dNTPase controlling dNTP/deoxynucleoside homeostasis in mammalian cells. Read More

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February 2021

Chaperone-Assisted Mitotic Actin Remodeling by BAG3 and HSPB8 Involves the Deacetylase HDAC6 and Its Substrate Cortactin.

Int J Mol Sci 2020 Dec 25;22(1). Epub 2020 Dec 25.

Centre de Recherche sur le Cancer, Université Laval, Québec, QC G1R 3S3, Canada.

The fidelity of actin dynamics relies on protein quality control, but the underlying molecular mechanisms are poorly defined. During mitosis, the cochaperone BCL2-associated athanogene 3 (BAG3) modulates cell rounding, cortex stability, spindle orientation, and chromosome segregation. Mitotic BAG3 shows enhanced interactions with its preferred chaperone partner HSPB8, the autophagic adaptor p62/SQSTM1, and HDAC6, a deacetylase with cytoskeletal substrates. Read More

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December 2020

The phosphatase inhibitor Sds23 promotes symmetric spindle positioning in fission yeast.

Cytoskeleton (Hoboken) 2020 Dec 14;77(12):544-557. Epub 2020 Dec 14.

Department of Biochemistry and Cell Biology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.

A hallmark of cell division in eukaryotic cells is the formation and elongation of a microtubule (MT)-based mitotic spindle. Proper positioning of the spindle is critical to ensure equal segregation of the genetic material to the resulting daughter cells. Both the timing of spindle elongation and constriction of the actomyosin contractile ring must be precisely coordinated to prevent missegregation or damage to the genetic material during cellular division. Read More

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December 2020

SAC during early cell divisions: Sacrificing fidelity over timely division, regulated differently across organisms: Chromosome alignment and segregation are left unsupervised from the onset of development until checkpoint activity is acquired, varying from species to species.

Bioessays 2021 Mar 30;43(3):e2000174. Epub 2020 Nov 30.

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

Early embryogenesis is marked by a frail Spindle Assembly Checkpoint (SAC). The time of SAC acquisition varies depending on the species, cell size or a yet to be uncovered developmental timer. This means that for a specific number of divisions, biorientation of sister chromatids occurs unsupervised. Read More

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ATE1-Mediated Post-Translational Arginylation Is an Essential Regulator of Eukaryotic Cellular Homeostasis.

ACS Chem Biol 2020 12 23;15(12):3073-3085. Epub 2020 Nov 23.

Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, Maryland 21250, United States.

Arginylation is a protein post-translational modification catalyzed by arginyl-tRNA transferases (ATE1s), which are critical enzymes conserved across all eukaryotes. Arginylation is a key step in the Arg N-degron pathway, a hierarchical cellular signaling pathway that links the ubiquitin-dependent degradation of a protein to the identity of its N-terminal amino acid side chain. The fidelity of ATE1-catalyzed arginylation is imperative, as this post-translational modification regulates several essential biological processes such as cardiovascular maturation, chromosomal segregation, and even the stress response. Read More

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December 2020

Cell division requires RNA eviction from condensing chromosomes.

J Cell Biol 2020 11;219(11)

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

During mitosis, the genome is transformed from a decondensed, transcriptionally active state to a highly condensed, transcriptionally inactive state. Mitotic chromosome reorganization is marked by the general attenuation of transcription on chromosome arms, yet how the cell regulates nuclear and chromatin-associated RNAs after chromosome condensation and nuclear envelope breakdown is unknown. SAF-A/hnRNPU is an abundant nuclear protein with RNA-to-DNA tethering activity, coordinated by two spatially distinct nucleic acid-binding domains. Read More

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November 2020

The EB1-Kinesin-14 complex is required for efficient metaphase spindle assembly and kinetochore bi-orientation.

J Cell Biol 2020 12;219(12)

Department of Molecular Genetics, Faculty of Biology, Center of Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.

Kinesin-14s are conserved molecular motors required for high-fidelity chromosome segregation, but their specific contributions to spindle function have not been fully defined. Here, we show that key functions of budding yeast Kinesin-14 Cik1-Kar3 are accomplished in a complex with Bim1 (yeast EB1). Genetic complementation of mitotic phenotypes identifies a novel KLTF peptide motif in the Cik1 N-terminus. Read More

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December 2020

The Geometry of Limb Motor Innervation is Controlled by the Dorsal-Ventral Compartment Boundary in the Chick Limbless Mutant.

Neuroscience 2020 12 8;450:29-47. Epub 2020 Oct 8.

Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA; Center for Motor Neuron Biology and Disease, Columbia University Medical Center, New York, NY 10032, USA; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA. Electronic address:

Precise control of limb muscles, and ultimately of limb movement, requires accurate motor innervation. Motor innervation of the vertebrate limb is established by sequential selection of trajectories at successive decision points. Motor axons of the lateral motor column (LMC) segregate at the base of the limb into two groups that execute a choice between dorsal and ventral tissue: medial LMC axons innervate the ventral limb, whereas lateral LMC axons innervate the dorsal limb. Read More

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December 2020

Centromere strength: just a sense of proportion.

Mol Cell Oncol 2020 7;7(4):1742063. Epub 2020 Apr 7.

Institut Curie, PSL Research University, Paris, France.

The overall structure and composition of human centromeres have been well reported, but how these elements vary between individual chromosomes and influence the chromosome-specific behavior during mitosis remains untested. In our study, we discover the existence of heterogeneity of centromeric DNA features that dictates the chromosome segregation fidelity during mitosis. Read More

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Atypical meiosis can be adaptive in outcrossed due to meiotic drivers.

Elife 2020 08 13;9. Epub 2020 Aug 13.

Stowers Institute for Medical Research, Kansas City, United States.

Killer meiotic drivers are genetic parasites that destroy 'sibling' gametes lacking the driver allele. The fitness costs of drive can lead to selection of unlinked suppressors. This suppression could involve evolutionary tradeoffs that compromise gametogenesis and contribute to infertility. Read More

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Deubiquitylase UCHL3 regulates bi-orientation and segregation of chromosomes during mitosis.

FASEB J 2020 09 1;34(9):12751-12767. Epub 2020 Aug 1.

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Department of development and stem cells, Illkirch, France.

Equal segregation of chromosomes during mitosis ensures euploidy of daughter cells. Defects in this process may result in an imbalance in the chromosomal composition and cellular transformation. Proteolytic and non-proteolytic ubiquitylation pathways ensure directionality and fidelity of mitotic progression but specific mitotic functions of deubiquitylating enzymes (DUBs) remain less studied. Read More

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September 2020

The Error-Prone Kinetochore-Microtubule Attachments During Meiosis I in Vitrified Oocytes.

Front Cell Dev Biol 2020 9;8:621. Epub 2020 Jul 9.

National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China.

Oocytes vitrification is frequently applied in assisted reproductive technologies. However, chromosomes segregation was error-prone during meiosis maturation of vitrified oocytes. The fidelity of chromosomes segregation depends on the correct kinetochore-microtubule attachments (KT-MTs). Read More

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Germline engineering of the chicken genome using CRISPR/Cas9 by transfection of PGCs.

Anim Biotechnol 2020 Jul 24:1-10. Epub 2020 Jul 24.

Australian Centre for Disease Preparedness, CSIRO Health and Biosecurity, Geelong, Australia.

Development of simple and readily adoptable methods to mediate germline engineering of the chicken genome will have many applications in research, agriculture and industrial biotechnology. We report germline targeting of the endogenous chicken Interferon Alpha and Beta Receptor Subunit 1 (IFNAR1) gene by transgenic expression of the high-fidelity Cas9 (Cas9-HF1) and guide RNAs (gRNAs) in chickens. First, we developed a Tol2 transposon vector carrying Cas9-HF1, IFNAR1-gRNAs (IF-gRNAs) and green fluorescent protein (GFP) transgenes (pTgRCG) and validated in chicken fibroblast DF1 cells. Read More

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Optimized high-fidelity 3DPCR to assess potential mitochondrial targeting by activation-induced cytidine deaminase.

FEBS Open Bio 2020 Sep 13;10(9):1782-1792. Epub 2020 Aug 13.

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Research Center of Stomatology, Xi'an Jiaotong University College of Stomatology, Xi'an, China.

Activation-induced cytidine deaminase (AID) initiates somatic hypermutation and class switch recombination of immunoglobulin genes in B cells, whereas off-targeted AID activity contributes to oncogenic mutations and chromosomal translocations associated with B cell malignancies. Paradoxically, only a minority of AID is allowed to access the nuclear genome, but the majority of AID is retained in the cytoplasm. It is unknown whether cytoplasmic AID can access and target the mitochondrial genome [mitochondrial DNA (mtDNA)]. Read More

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September 2020

H3K9me3 maintenance on a human artificial chromosome is required for segregation but not centromere epigenetic memory.

J Cell Sci 2020 07 24;133(14). Epub 2020 Jul 24.

Wellcome Trust Centre for Cell Biology, Edinburgh, UK

Most eukaryotic centromeres are located within heterochromatic regions. Paradoxically, heterochromatin can also antagonize centromere formation, and some centromeres lack it altogether. In order to investigate the importance of heterochromatin at centromeres, we used epigenetic engineering of a synthetic alphoid human artificial chromosome (HAC), to which chimeric proteins can be targeted. Read More

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Advances and surprises in a decade of oocyte meiosis research.

Binyam Mogessie

Essays Biochem 2020 09;64(2):263-275

School of Biochemistry, University of Bristol, Bristol BS8 1TD, U.K.

Eggs are produced from progenitor oocytes through meiotic cell division. Fidelity of meiosis is critical for healthy embryogenesis - fertilisation of aneuploid eggs that contain the wrong number of chromosomes is a leading cause of genetic disorders including Down's syndrome, human embryo deaths and infertility. Incidence of meiosis-related oocyte and egg aneuploidies increases dramatically with advancing maternal age, which further complicates the 'meiosis problem'. Read More

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September 2020

Auto-inhibition of Mif2/CENP-C ensures centromere-dependent kinetochore assembly in budding yeast.

EMBO J 2020 07 9;39(14):e102938. Epub 2020 Jun 9.

Department of Molecular Genetics, Faculty of Biology, Center of Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.

Kinetochores are chromatin-bound multi-protein complexes that allow high-fidelity chromosome segregation during mitosis and meiosis. Kinetochore assembly is exclusively initiated at chromatin containing Cse4/CENP-A nucleosomes. The molecular mechanisms ensuring that subcomplexes assemble efficiently into kinetochores only at centromeres, but not anywhere else, are incompletely understood. Read More

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Emerging themes in cohesin cancer biology.

Todd Waldman

Nat Rev Cancer 2020 09 8;20(9):504-515. Epub 2020 Jun 8.

Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC, USA.

Mutations of the cohesin complex in human cancer were first discovered ~10 years ago. Since then, researchers worldwide have demonstrated that cohesin is among the most commonly mutated protein complexes in cancer. Inactivating mutations in genes encoding cohesin subunits are common in bladder cancers, paediatric sarcomas, leukaemias, brain tumours and other cancer types. Read More

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September 2020

Stepping Up, Stepping Out: A program description and preliminary findings.

Psychol Serv 2020 May 25. Epub 2020 May 25.

Corizon Health, Inc.

Research on the effects of restricted housing on inmate well-being indicates mild to moderate psychological effects and barriers opportunities for treatment and positive growth. Yet, there are few interventions tailored both to the needs of this high-risk population and to the institutional constraints of their environment. Given the financial and safety burdens associated with housing someone in segregation compared to the general population, correctional psychology should focus on developing programs that work. Read More

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