In the pre-implantation embryo, aneuploidy resulting from chromosome segregation error is considered responsible for pregnancy loss. However, only a few studies have examined the relationship between chromosome segregation errors during early cleavage and development. Here, we evaluated this relationship by live-cell imaging using the histone H2B-mCherry probe and subsequent single blastocyst transfer using mouse embryos obtained by in vitro fertilization. We showed that some embryos exhibiting early chromosomal segregation error and formation of micronuclei retained their developmental potential; however, the error affected the blastocyst/arrest ratio. Further, single-cell sequencing after live-cell imaging revealed that all embryos exhibiting micronuclei formation during 1st mitosis showed aneuploidy at the 2-cell stage. These results suggest that early chromosome segregation error causing micronuclei formation affects ploidy and development to blastocyst but does not necessarily cause developmental
程金妹.,李建.,汤济鑫.,郝晓霞.,王志鹏.,...&刘以训.(2017).Merotelic Kinetochore Attachment in Oocyte Meiosis II Causes Sister Chromatids Segregation Errors in Aged Mice.Cell Cycle,16(15),1404-1413 ...
Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here we show that activation of the DNA damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and Plk1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or Chk2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, DDR ...
Studies of chromosome organization in bacterial cells show that the chromosome is an exquisitely organized and dynamic structure (reviewed recently in Thanbichler et al., 2005). Chromosome segregation in bacteria does not occur all at once but in sequential phases (Lau et al., 2003; Viollier et al., 2004; Bates and Kleckner, 2005; Nielsen et al., 2006). After replication at mid-cell, the origin region (oriC) is rapidly segregated outward. The speed at which this occurs (reviewed in Gordon and Wright, 2000) rules out passive models for bacterial chromosome segregation, which proposed that outward cellular growth could drive the movement of a fixed chromosome. As the loci of the chromosome are replicated, they are moved outward to the poles in a sequential fashion (Lau et al., 2003; Viollier et al., 2004; Bates and Kleckner, 2005; Nielsen et al., 2006). In Escherichia coli, there may be a period of sister chromosome cohesion between duplication and subsequent segregation, although its length is ...
The improper partitioning of chromosomes is responsible for a many human maladies. Errors in mitotic chromosome segregation contribute to the development of cancer while errors in meiosis are the leading cause of birth defects and infertility. Proper chromosome segregation requires the co-ordination of chromosome behavior with other cellular events, and the assembly of a functional machine to move the chromosomes to the right place at the right time in the cell cycle. The research in our laboratory is focused on both the regulatory and mechanical aspects of chromosome behavior. Our projects primarily use the yeast, Saccharomyces cerevisiae, as a model to elucidate conserved aspects of eukaryotic chromosome biology. Our goal is to elucidate fundamentals of chromosome behavior that will provide insights into the origins of chromosome segregation errors in humans.. Our laboratory is involved in two major projects. Slk19 is a bi-functional protein. Slk19 is a member of the FEAR signaling pathway ...
Mitotic chromosome malsegregation produces aneuploidy and genome instability. An increasing number of studies have shown that abnormalities such as aneuploidy and whole-chromosome loss of heterozygosity are commonly present in tumor cells. This suggests that chromosome instability and aneuploidy may play a critical role in tumor development and progression ( Sen, 2000).. The integrity of the cell and of its genome and the correct accomplishment of cellular processes depend on the existence of control points in the cell cycle. These control mechanisms, called `checkpoints, inhibit the transition to the next cell cycle phase if the events of the previous phase have not been correctly executed. A mitotic checkpoint has been identified that controls the metaphase to anaphase transition. A large number of studies have demonstrated that in vertebrates the kinetochore plays an active role in the mitotic checkpoint pathway and that microtubule accumulation at the kinetochore and/or tension that ...
Research done in Prof. Sharon Bickels lab has demonstrated that oxidative damage causes a premature loss of sister chromatid cohesion and an increase in chromosome segregation errors in Drosophila oocytes during meiosis. In women, the probability of miscarriage or Down Syndrome increases dramatically with age. Studies of maternal age effect indicate that errors in female meiosis contribute significantly to this age-related effect. The research done by the Bickel lab demonstrates that if oxidative damage contributes to maternal age effect then reducing oxidative damage could be a strategy for reducing chromosome segregation errors during meiosis.. Professor Sharon Bickel, MCB graduate student Adrienne Perkins, Class of 2013 undergraduate researcher Thomas Das and second year MCB graduate student Lauren Panzera contributed to this work. These findings were published in the Proceeding of the National Academy of Sciences: http://www.pnas.org/content/early/2016/10/12/1612047113.full ...
Cells possessing the incorrect number of chromosomes (referred to as aneuploid) can arise as a result of chromosome mis-segregation. Prevention of aneuploidy is especially important in germ cells, as these cells pass genetic information to the next generation, but also in pluripotent cells as these give rise to all tissues and cells of the offspring, including germ cells. Aneuploid conceptions have a detrimental effect on pregnancy outcomes, are surprisingly common in humans (estimated 10-30%), and are a leading cause of miscarriage and developmental disorders. In both meiosis and mitosis, accurate chromosome segregation relies on the correct orientation of sister chromatids during metaphase, which ensures bipolar spindle attachment. Newly replicated sister chromatids are able to align properly on the spindle due to cohesion holding them together. The protein complex responsible for sister chromatid cohesion (SCC) is called cohesin, and has specific subunits depending on its particular role. The ...
Cell cycle: a series of events that occur in cells leading up to their division and replication. Its divided into two main parts, Interphase and a Mitotic or M phase. Interphase is further subdivided into three phases including: G1, S and G2. Each phase has different events occurring within them Cell division: an essential process that occurs in almost all living things. It is characterised by the separation of a cell into two daughter cells. In metazoans, it involves separation of the nucleus and of the cytoplasm Centromere: Confined portion of a mitotic chromosome where sister chromatids are attached and from which kinetochore fibers extend toward a spindle pole. It is essential for correct chromosome segregation during mitosis Chromatin:it is made up of histones, non-histone proteins and DNA which condenses to form eukaryotic chromosomes Chromosome: a single molecule of DNA which is highly organised and tightly packed around proteins (histones) Chromosomal segregation: process by which ...
Cell cycle: a series of events that occur in cells leading up to their division and replication. Its divided into two main parts, Interphase and a Mitotic or M phase. Interphase is further subdivided into three phases including: G1, S and G2. Each phase has different events occurring within them Cell division: an essential process that occurs in almost all living things. It is characterised by the separation of a cell into two daughter cells. In metazoans, it involves separation of the nucleus and of the cytoplasm Centromere: Confined portion of a mitotic chromosome where sister chromatids are attached and from which kinetochore fibers extend toward a spindle pole. It is essential for correct chromosome segregation during mitosis Chromatin:it is made up of histones, non-histone proteins and DNA which condenses to form eukaryotic chromosomes Chromosome: a single molecule of DNA which is highly organised and tightly packed around proteins (histones) Chromosomal segregation: process by which ...
Chromosome segregation and cell division are essential, highly ordered processes that depend on numerous protein complexes. Results from recent RNA interference screens indicate that the identity and composition of these protein complexes is incompletely understood. Using gene tagging on bacterial artificial chromosomes, protein localization, and tandem-affinity purification-mass spectrometry, the MitoCheck consortium has analyzed about 100 human protein complexes, many of which had not or had only incompletely been characterized. This work has led to the discovery of previously unknown, evolutionarily conserved subunits of the anaphase-promoting complex and the gamma-tubulin ring complex--large complexes that are essential for spindle assembly and chromosome segregation. The approaches we describe here are generally applicable to high-throughput follow-up analyses of phenotypic screens in mammalian cells ...
TY - BOOK ID - 21915 TI - Mechanisms of Mitotic Chromosome Segregation AU - J. Richard McIntosh PY - 2017 SN - 9783038424031 9783038424024 DB - DOAB KW - chromosome segregation, microtubule dynamics, kinetochore, centrosome, genome stability, Cell division, Cell cycle, Cell reproduction, Checkpoints, Cell motility, Inheritance, Microtubules, Cytoskeleton, Cell regulation, Down Syndrome, Trisomies UR - https://www.doabooks.org/doab?func=search&query=rid:21915 AB - This book describes current knowledge about the mechanisms by which cells segregate their already duplicated chromosomes in preparation for cell division. Experts in the field treat several important aspects of this subject: (1) the history of research on mitotic mechanisms, to serve as a background; (2) assembly of the mitotic spindle; (3) Kinetochore assembly and function; (4) the mechanisms of chromosome congression to the metaphase plate; (5) the spindle assembly checkpoint; (6) mechanisms to avoid and correct erroneous chromosome ...
Many cancers have extremely high rates of chromosomal instability (CIN). Some cancers have chromosome segregation errors in every cell division, which would be detrimental to the growth of normal cells. Little is known about how cancers are able to thrive with high levels of CIN. We aim to determine how cells evolve to cope with CIN by creating a model system for persistent chromosomal instability in budding yeast. What types of mutations allow cells to adapt to a constantly shifting genomic content? What are the direct effects of CIN and aneuploidy on the health and viability of cells?. ...
The research interests of the participating groups are listed below. Follow the links for more detailed information.. Gustav Ammerer: Signal transduction and transcriptional regulation in yeast. Oliver Bell: Editing the epigenome: plasticity and memory of chromatin structure. Frederic Berger: Histone variants in chromatin structure. Christopher Campbell: Chromosome dynamics. Alexander Dammermann: Centriole assembly and function. Daniel Gerlich: Cytoskeletal and membrane dynamics in cell division. Juraj Gregan: Chromosome segregation during mitosis and meiosis. Verena Jantsch-Plunger: Faithful chromosome segregation in C. elegans meiosis. Franz Klein: Deconstructing the meiotic (yeast) chromosome. Josef Loidl: Meiotic chromosome pairing and recombination. Ortrun Mittelsten Scheid: Epigenetic changes in plants ...
Control of sister chromatid cohesion/separation is critical to ensure faithful chromosome segregation during mitosis and meiosis. Failures in this mechanism during mitosis often lead to aneuploidy and chromosome instability, a major cause of cancer, while failures during meiosis promote miscarriage, birth defects, and infertility in humans. A key protagonist in this control is the cohesin complex, which are composed essentially by four subunits, two of them, called Smc1 and Smc3 (Structural maintenance of chromosomes), are members of a highly conserved protein family also found in prokaryotes and are implicated in various functions related to DNA dynamics, dose compensation, chromosome condensation, recombination, etc. The other two subunits are specific to eukaryotes and, depending on the organism, are termed Scc1/Rad21 or Scc3/STAG, the former mainly for yeast and the latter in higher eukaryotes. In addition to their function in chromatid cohesion during chromosome segregation, our previous ...
DNA replication, transcription, repair, epigenetic inheritance, and chromosome segregation are all processes critical for maintaining cellular viability. In euk...
Author: Hutchins, J. R. A. et al.; Genre: Journal Article; Published in Print: 2010-04-30; Title: Systematic analysis of human protein complexes identifies chromosome segregation proteins.
Results: We show that the SMC4 subunit of condensin is encoded by the essential gluon locus in Drosophila. DmSMC4 contains all the conserved domains present in other members of the structural-maintenance-of-chromosomes protein family. DmSMC4 is both nuclear and cytoplasmic during interphase, concentrates on chromatin during prophase, and localizes to the axial chromosome core at metaphase and anaphase. During decondensation in telophase, most of the DmSMC4 leaves the chromosomes. An examination of gluon mutations indicates that SMC4 is required for chromosome condensation and segregation during different developmental stages. A detailed analysis of mitotic chromosome structure in mutant cells indicates that although the longitudinal axis can be shortened normally, sister chromatid resolution is strikingly disrupted. This phenotype then leads to severe chromosome segregation defects, chromosome breakage, and apoptosis ...
Journal of Cell Science is pleased to be a part of the new and exciting Review Commons initiative, launched by EMBO and ASAPbio. Streamlining the publishing process, Review Commons enables high-quality peer review to take place before journal submission. Papers submitted to Review Commons will be assessed independently of any journal, focusing solely on the papers scientific rigor and merit.. ...
Mutations in CDCA7 and HELLS that respectively encode a CXXC-type zinc finger protein and an SNF2 family chromatin remodeler cause immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome types 3 and 4. Here, we demonstrate that the classical nonhomologous end joining (C-NHEJ) proteins Ku80 and Ku70, as well as HELLS, coimmunoprecipitated with CDCA7. The coimmunoprecipitation of the repair proteins was sensitive to nuclease treatment and an ICF3 mutation in CDCA7 that impairs its chromatin binding. The functional importance of these interactions was strongly suggested by the compromised C-NHEJ activity and significant delay in Ku80 accumulation at DNA damage sites in CDCA7- and HELLS-deficient HEK293 cells. Consistent with the repair defect, these cells displayed increased apoptosis, abnormal chromosome segregation, aneuploidy, centrosome amplification, and significant accumulation of γH2AX signals. Although less prominent, cells with mutations in the other ICF genes ...
Mutations in CDCA7 and HELLS that respectively encode a CXXC-type zinc finger protein and an SNF2 family chromatin remodeler cause immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome types 3 and 4. Here, we demonstrate that the classical nonhomologous end joining (C-NHEJ) proteins Ku80 and Ku70, as well as HELLS, coimmunoprecipitated with CDCA7. The coimmunoprecipitation of the repair proteins was sensitive to nuclease treatment and an ICF3 mutation in CDCA7 that impairs its chromatin binding. The functional importance of these interactions was strongly suggested by the compromised C-NHEJ activity and significant delay in Ku80 accumulation at DNA damage sites in CDCA7- and HELLS-deficient HEK293 cells. Consistent with the repair defect, these cells displayed increased apoptosis, abnormal chromosome segregation, aneuploidy, centrosome amplification, and significant accumulation of γH2AX signals. Although less prominent, cells with mutations in the other ICF genes ...
Mutations in CDCA7 and HELLS that respectively encode a CXXC-type zinc finger protein and an SNF2 family chromatin remodeler cause immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome types 3 and 4. Here, we demonstrate that the classical nonhomologous end joining (C-NHEJ) proteins Ku80 and Ku70, as well as HELLS, coimmunoprecipitated with CDCA7. The coimmunoprecipitation of the repair proteins was sensitive to nuclease treatment and an ICF3 mutation in CDCA7 that impairs its chromatin binding. The functional importance of these interactions was strongly suggested by the compromised C-NHEJ activity and significant delay in Ku80 accumulation at DNA damage sites in CDCA7- and HELLS-deficient HEK293 cells. Consistent with the repair defect, these cells displayed increased apoptosis, abnormal chromosome segregation, aneuploidy, centrosome amplification, and significant accumulation of γH2AX signals. Although less prominent, cells with mutations in the other ICF genes ...
MIT biologists have discovered that the environment surrounding a cell plays an integral role in its ability to accurately segregate its chromosomes.
Chromosome segregation during male meiosis is tailored to rapidly generate multitudes of sperm. Little is known about mechanisms that efficiently partition chromosomes to produce sperm. Using live imaging and tomographic reconstructions of spermatocyte meiotic spindles inCaenorhabditis elegans, we find the lagging X chromosome, a distinctive feature of anaphase I inC. elegans males, is due to lack...
early embryonic: 3/5 embryos show spindle related defects, in one of the cases the spindle is hardly visible, in others centration fails or is inaccurate, rocking is missing. This leads to chromosome segregation defects in two of the embryos ...
In a body, every single cell has the same number of chromosomes. This is because when a cell divides, the replicated chromatids are equally segregated into daughter cells. But, the first meiotic division is a clear exception. This division segregates maternal and paternal chromosomes for production of eggs and sperms, which are the origin of a new life. What is the story behind this division?. Read More ...
If you have a question about this talk, please contact Ross Waller.. Host: Mark Carrington. Abstract not available. This talk is part of the Parasitology Seminars series.. ...
An intricate network of proteins ensures the faithful transmission of genetic information through cell generations. The Structural Maintenance of Chromosomes (SMC) protein complex family plays a pivotal role in maintaining genome stability. Initially, the three eukaryotic SMC complexes, cohesin, condensin and Smc5/6 complex (Smc5/6) were identified for their functions in chromosome cohesion, condensation and recombination. Later, it was shown that SMC complexes also control replication and transcription. Another important group of proteins involved in the maintenance of genome stability are the topoisomerases. These enzymes control DNA topology to ensure faithful replication, transcription and chromosome segregation ...
Cohesin is a conserved multisubunit protein complex with diverse cellular roles, making key contributions to the coordination of chromosome segregation, the DNA damage response and chromatin regulation by epigenetic mechanisms. Much has been learned in recent years about the roles of cohesin in a ph …
Michael Goldberg is a Professor in the Department of Molecular Biology and Genetics. Dr. Goldberg is a member of the Graduate Field of Genetics, Genomics and Development and the Graduate Field of Biochemistry, Molecular, and Cell Biology. The Goldberg lab studies the molecular mechanisms which ensure accurate chromosome segregation and other chromosome behaviors.
NIMA in A. nidulans has known functions in G2-M checkpoint control, as does at least one of its mammalian orthologs, Nek2. Nek2 phosphorylates the kinetochore-associated mitotic regulator protein Hec1 and is therefore crucial for faithful chromosome segregation to daughter cells (13) . Our data suggest that Nek1 may be important for sensing, responding to, or repairing DNA damage and thereby for regulating apoptosis and cellular proliferation after injury. When Nek1 is mutated or when its up-regulation is otherwise insufficient, cells are more likely to die aberrantly or fail to proliferate when they normally should. Some cells surviving the insult would also be more likely to pass subtle mutations on to their daughters, which could then accumulate activating oncogenic or inactivating tumor suppressor mutations. Up-regulation of Nek1 may be a defensive response to cellular and DNA injury, a response to prevent excessive or unscheduled apoptosis. If so, we predict that Nek1 might be overexpressed ...
Classical simulations are described of the fully relaxed surface lattice structures of the five lowest-index planes of α-Al20 3 and the resulting crystal morphology. The surface coverage by yttrium and magnesium as a function of temperature is evaluated on the basis of a non-Arrhenius isotherm and calculated heats of surface segregation. The calculated morphology, surface coverages and heats of segregation are compared with experiment. A quantum simulation of a relaxed {0001} surface is presented and the surface structure and energy compared with the classical results. Estimates are made of the adsorption energy of HF at the {0001} surface. ...
Diagnostic screening allows medical practitioners to identify diseases caused by defective chromosomes, genes or proteins. This screening can occur pre-natally (before birth), pre-symptomatically (before symptoms develop) or be used to confirm a suspected diagnosis. ...
Self-Placing Concrete segregation set of tests - Béton Auto-Plaçant ensemble dessais de ségrégation (). The Forney Column Segregation Test Set contains everything needed to determine the potential segregation of coarse aggregate in SCC mixtures tes
Most people have a passing knowledge of the food they eat, and perhaps how it gets digested. As with all human body systems, however, details of the digestive or gastrointestinal (GI) tract-including the incredibly rich microbial flora found at the last portion of the small intestine and the entire large intestine-are an amazing testimony to creation.. Indeed, on a given day the bacterial population within the human colon usually doubles at least once. This means the common Escherichia coli (E. coli) must replicate (duplicate) its circular chromosome in just 20 short minutes.. The replication of millions of base pairs of DNA is a daunting task in such a small area. The E. coli chromosome must spin at the equivalent of 300 revolutions per second as it makes a second chromosome for upcoming cell division.. A host of unique and diverse bacteria inhabit the large intestine-over 400 bacterial species-and most of them are anaerobic (living in the absence of free oxygen) and are concerned with the ...
The cohesin complex is responsible for the fidelity of chromosomal segregation during mitosis. It consists of four core subunits namely Rad21/Mcd1/Sccl, Smc1, Smc3 and one of the yeast Scc3 orthologs SA1 or SA2. Sister ...
Biochemist Dr Lakxmi Subramanian looks at chromosome segregation during cell division to find out how and why things go wrong even before a child is born
CP000529.PE67 Location/Qualifiers FT CDS 70682..71617 FT /codon_start=1 FT /transl_table=11 FT /locus_tag="Pnap_0068" FT /product="chromosome segregation DNA-binding protein" FT /note="TIGRFAM: parB-like partition proteins; PFAM: ParB FT domain protein nuclease; KEGG: pol:Bpro_0078 ParB-like FT partition proteins" FT /db_xref="EnsemblGenomes-Gn:Pnap_0068" FT /db_xref="EnsemblGenomes-Tr:ABM35394" FT /db_xref="GOA:A1VIB6" FT /db_xref="InterPro:IPR003115" FT /db_xref="InterPro:IPR004437" FT /db_xref="InterPro:IPR036086" FT /db_xref="InterPro:IPR041468" FT /db_xref="UniProtKB/TrEMBL:A1VIB6" FT /protein_id="ABM35394.1" FT /translation="MVTKKQKGLGRGLEALLGPKVDESPEAANALIAASSPGLPASLLL FT DDLVPGQYQPRTRMDEGALYELAESIKVQGIMQPILVRRLKSGSNSGKYEIIAGERRFR FT AARLAGLDSLPVLIRDVPDESAAAMSLIENIQREDLNPLEEAQGLQRLVKEFGLTHELA FT AQAVGRSRSAASNLLRLLNLADPVQTMLMAGDLDMGHARALLALDRATQITAANQITAK FT KLSVREAESLVKKLGSEFSLTPNKAPPEKSRDTRRVEEELADLLMAEVQVRIKKQVKRN FT GKREDVGELAIQFASLDEVNGLIERLRRTA" MVTKKQKGLG RGLEALLGPK VDESPEAANA ...
Hutchins JR, Toyoda Y, Hegemann B, Poser I, Hériché JK, Sykora MM, Augsburg M, Hudecz O, Buschhorn BA, Bulkescher J, Conrad C, Comartin D, Schleiffer A, Sarov M, Pozniakovsky A, Slabicki MM, Schloissnig S, Steinmacher I, Leuschner M, Ssykor A, Lawo S, Pelletier L, Stark H, Nasmyth K, Ellenberg J, Durbin R, Buchholz F, Mechtler K, Hyman AA, Peters JM. (2010). Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science 328(5978):593-599. doi: 10.1126/science. ...
Segregation in a cross between strains carrying a transposed segment.In this example, two haploid parental strains harbor a particular genomic region (black) on
The Axon framework is a Java implementation of the Command and Query Responsibility Segregation. InfoQ talked with its creator, Allard Buijze, to find out more.
Errors in chromosome segregation in mammalian oocytes lead to aneuploid eggs that are developmentally compromised. In mitotic cells, mitotic centromere associated kinesin (MCAK; KIF2C) prevents chromosome segregation errors by detaching incorrect microtubule-kinetochore interactions. Here, we examine whether MCAK is involved in spindle function in mouse oocyte meiosis I, and whether MCAK is necessary to prevent chromosome segregation errors. We find that MCAK is recruited to centromeres, kinetochores and chromosome arms in mid-meiosis I, and that MCAK depletion, or inhibition using a dominant-negative construct, causes chromosome misalignment. However, the majority of oocytes complete meiosis I and the resulting eggs retain the correct number of chromosomes. Moreover, MCAK-depleted oocytes can recover from mono-orientation of homologous kinetochores in mid-meiosis I to segregate chromosomes correctly. Thus, MCAK contributes to chromosome alignment in meiosis I, but is not necessary for ...
Heterochromatin protein 1 is associated with centromeric heterochromatin in Drosophila, mice, and humans. Loss of function mutations in the gene encoding heterochromatin protein 1 in Drosophila, Suppressor of variegation2-5, decrease the mosaic repression observed for euchromatic genes that have been juxtaposed to centromeric heterochromatin. These heterochromatin protein 1 mutations not only suppress this position-effect variegation, but also cause recessive embryonic lethality. In this study, we analyze the latter phenotype in the hope of gaining insight into heterochromatin function. In our analyses of four alleles of Suppressor of variegation2-5, the lethality was found to be associated with defects in chromosome morphology and segregation. While some of these defects are seen throughout embryonic development, both the frequency and severity of the defects are greatest between cycles 10 and 14 when zygotic transcription of the Suppressor of variegation2-5 gene apparently begins. By this time ...
Lagging chromosomes during anaphase are an easily assayed and therefore commonly reported mitotic defect. However, in most cases, the mechanisms that give rise to lagging chromosomes are unknown. Lagging chromosomes can be caused by asbestos fibers (Hersterberg and Barrett, 1985), elevated ras p21 expression (Hagag et al., 1990), carcinogens such as diethylstilbestrol (Schiffmann and De Boni, 1991), and inherited genetic conditions such as Roberts syndrome (Jabs et al., 1991). Chromosomes, chromatids, and chromosome fragments that do not segregate properly often end up spatially separated from the bulk of the chromosomes and will reform a separate nuclear envelope after mitosis is completed. This results in a cell containing micronuclei. Sometimes these cells are described as multinucleate. Severe chromosome segregation defects will in turn inhibit cytokinesis giving rise to truly multinucleate cells (Schultz and Onfelt, 1994). The mechanism by which these diverse agents disrupt anaphase ...
Accurate segregation of meiotic chromosomes requires that sister-chromatids remain physically associated from the time of their synthesis during S phase until they segregate toward opposite poles at anaphase II. In Drosophila melanogaster meiosis, physical association of sister chromatids, known as sister-chromatid cohesion, requires the protein product of the orientation disruptor (ord) gene. Genetic and cytological analyses of ord mutants indicate that sister chromatids separate precociously in the absence of ORD activity, resulting in random chromosome segregation during both meiotic divisions. To understand the molecular basis of ORD activity more fully, we localized ORD protein in Drosophila spermatocytes using immunofluorescence and demonstrate that ORD associates with centromeres of meiotic chromosomes from early G2 through anaphase II. Maintenance of ORD at centromeres until anaphase II requires functional MEI-S332 protein, as centromeric ORD signal disappears during anaphase I in ...
The IPL1 gene is required for high-fidelity chromosome segregation in the budding yeast Saccharomyces cerevisiae. Conditional ipl1ts mutants missegregate chromosomes severely at 37 degrees C. Here, we report that IPL1 encodes an essential putative protein kinase whose function is required during the later part of each cell cycle. At 26 degrees C, the permissive growth temperature, ipl1 mutant cells are defective in the recovery from a transient G2/M-phase arrest caused by the antimicrotubule drug nocodazole. In an effort to identify additional gene products that participate with the Ipl1 protein kinase in regulating chromosome segregation in yeast, a truncated version of the previously identified DIS2S1/GLC7 gene was isolated as a dosage-dependent suppressor of ipl1ts mutations. DIS2S1/GLC7 is predicted to encode a catalytic subunit (PP1C) of type 1 protein phosphatase. Overexpression of the full-length DIS2S1/GLC7 gene results in chromosome missegregation in wild-type cells and exacerbates the ...
Mitosis is a key event in the life of a cell, where duplicated chromosomes are separated into the daughter cells. Defects associated with chromosome segregation can lead to aneuploidy, a hallmark of cancer. Chromosome segregation is achieved by the mitotic spindle, which is composed of microtubules (MTs), motors and microtubule associated protein (MAPs). Motors such as kinesins generate forces within the spindle while MAPs perform functions such as organize the spindle pole and maintain the bipolar spindle. Both motors and MAPs contribute to spindle mechanics. Here I used the relatively simple fission yeast to address how defects in spindle mechanics affect chromosome segregation. The metaphase spindle is maintained at a constant length by an antagonistic force-balance model yet how the regulation of metaphase spindle length contribute to subsequent chromosome segregation remains unexplored. To test the force-balance model, I applied gene deletion and fast microfluidic temperature-control with live-cell
Accurate chromosome segregation in mitosis is required to maintain genetic stability. hZwint-1 [human Zw10 (Zeste white 10)-interacting protein 1] is a kinetochore protein known to interact with the kinetochore checkpoint protein hZw10. hZw10, along with its partners Rod (Roughdeal) and hZwilch, form a complex which recruits dynein-dynactin and Mad1-Mad2 complexes to the kinetochore and are essential components of the mitotic checkpoint. hZwint-1 localizes to the kinetochore in prophase, before hZw10 localization, and remains at the kinetochore until anaphase, after hZw10 has dissociated. This difference in localization timing may reflect a role for hZwint-1 as a structural kinetochore protein. In addition to hZw10, we have found that hZwint-1 interacts with components of the conserved Ndc80 and Mis12 complexes in yeast two-hybrid and GST (glutathione transferase) pull-down assays. Furthermore, hZwint-1 was found to have stable FRAP (fluorescence recovery after photobleaching) dynamics similar ...
In humans, early embryo development is a complex process that consists of sequential events: oocyte maturation, fertilization, embryonic growth and implantation. Disruption of these highly regulated processes results in reproductive failure and infertility. This study characterizes and describes embryonic aneuploidy, mitochondrial content level and endometrial microbial environment related to reproductive competence, in particular instances in which failure results. To examine the molecular underpinnings of mammalian gamete and early embryo chromosome segregation, we established a comprehensive chromosomal screening (CCS) method for mice poly bodies, oocytes and embryos by the application of whole genome amplification (WGA) and next generation sequencing (NGS). First, we validated this approach using single mouse embryonic fibroblasts engineered to have stable trisomy 16. We further validated this method by identifying reciprocal chromosome segregation errors in the products of meiosis I (gamete and
Looking for chromosome congression? Find out information about chromosome congression. congression Explanation of chromosome congression