Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Chromosome Segregation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources
PubMed2001

[When chromosomal dynamics control cell division].

In most tumor cells a chromosomal instability leads to an abnormal chromosome number (aneuploidy). The mitotic checkpoint is essential for ensuring accurate chromosome segregation by allowing mitotic delay in response to a spindle defect. This checkpoint delays the onset of anaphase until all the chromosomes are correctly aligned on the mitotic spindle. When unattached kinetochores are present, the metaphase/anaphase transition is not allowed and the time available for chromosome-microtubule capture increases. Genes required for this delay were first identified in Saccharomyces cerevisiae (the MAD, BUB and MPS1 genes) and subsequently, homologs have been identified in higher eucaryotes showing that the spindle checkpoint pathway is highly conserved. The checkpoint functions by preventing an ubiquitin ligase called the anaphase-promoting complex/cyclosome (APC) from ubiquitinylating proteins whose destruction is required for anaphase onset.

Aneuploidy↗
PubMed2000

Centrosomal kinases, HsAIRK1 and HsAIRK3, are overexpressed in primary colorectal cancers.

Members of the recently identified family of Homo sapiens Aurora / Ipl1-related kinases (HsAIRKs), homologous to chromosome segregation kinases, fly Aurora and yeast Ipl1, are highly expressed during M phase, and have been suggested to regulate centrosome function, chromosome segregation, and cytokinesis. In the present study, immunohistochemical analyses were performed of HsAIRK1 and HsAIRK3 expression in 78 primary colorectal cancers and 36 colorectal adenomas as well as 15 normal colorectal specimens. In normal colon mucosa, some crypt cells showed weak positive staining in 10 and 12 out of 15 cases for HsAIRK1 and HsAIRK3, respectively, the remaining cases being negative. Elevated expression of HsAIRK1 was observed in 53 (67.9%) of the colorectal cancers, and of HsAIRK3 in 40 (51.3%). Furthermore, colorectal adenomas showed high expression of HsAIRK1 and HsAIRK3 in 11 (30.6%) and 7 (19.4%) cases, respectively, thus being intermediate between colorectal cancers and normal colorectal mucosa. Interestingly, HsAIRK1 overexpression was significantly associated with pT (primary tumor invasion) and p53 accumulation in colorectal cancers. There was no significant correlation between proliferating cell nuclear antigen-labeling index (PCNA-LI) and the levels of these proteins. The results suggest that overexpression of HsAIRK1 and HsAIRK3 might be involved in tumorigenesis and / or progression of colorectal cancers.

Adenoma↗
PubMed2003

Chromosome-wide control of meiotic crossing over in C. elegans.

A central event in sexual reproduction is the reduction in chromosome number that occurs at the meiosis I division. Most eukaryotes rely on crossing over between homologs, and the resulting chiasmata, to direct meiosis I chromosome segregation, yet make very few crossovers per chromosome pair. This indicates that meiotic recombination must be tightly regulated to ensure that each chromosome pair enjoys the crossover necessary to ensure correct segregation. Here, we investigate control of meiotic crossing over in Caenorhabditis elegans, which averages only one crossover per chromosome pair per meiosis, by constructing genetic maps of end-to-end fusions of whole chromosomes. Fusion of chromosomes removes the requirement for a crossover in each component chromosome segment and thereby reveals a propensity to restrict the number of crossovers such that pairs of fusion chromosomes composed of two or even three whole chromosomes enjoy but a single crossover in the majority of meioses. This regulation can operate over physical distances encompassing half the genome. The meiotic behavior of heterozygous fusion chromosomes further suggests that continuous meiotic chromosome axes, or structures that depend on properly assembled axes, may be important for crossover regulation.

Animals↗
PubMed1996

Expression of Bcl-xL and loss of p53 can cooperate to overcome a cell cycle checkpoint induced by mitotic spindle damage.

During somatic cell division, faithful chromosomal segregation must follow DNA replication to prevent aneuploidy or polyploidy. Damage to the mitotic spindle is one potential mechanism that interferes with chromosomal segregation. The accumulation of aneuploid or polyploid cells resulting from a disrupted mitotic spindle is presumably prevented by cell cycle checkpoint controls. In the course of studying cells that overexpress the apoptosis-inhibiting protein Bcl-xL, we found that these cells have an increased rate of spontaneous tetraploidization, suggesting that apoptosis may play an important role in eliminating cells that fail to complete mitosis properly. When cells expressing Bcl-xL are treated with mitotic spindle inhibitors, a significant percentage reinitiate DNA replication and become polyploid. Nevertheless, the majority of cells expressing Bcl-xL undergo a prolonged p53-dependent cell cycle arrest following mitotic spindle damage. Unexpectedly, p53 expression is not induced in mitosis, nor does it influence M-phase arrest. Instead, cells with mitotic spindle damage only transiently arrest in M phase, and despite failing to complete mitosis, appear to proceed to G1. During this subsequent growth factor-dependent phase, p53 is induced and mediates cell cycle arrest. In cells that do not overexpress Bcl-xL, elimination of the p53-dependent growth arrest with a dominant negative mutant also results in polyploidy after mitotic spindle damage, but under these conditions most cells die by apoptosis. Expression of Bcl-xL and abrogation of p53 cooperate to allow rapid and progressive polyploidization following mitotic spindle damage. Our results suggest that suppression of apoptosis by bcl-2-related genes and loss of p53 function can act cooperatively to contribute to genetic instability.

Apoptosis↗
PubMed2005

Mechanisms and chemical induction of aneuploidy in rodent germ cells.

The objective of this review is to suggest that the advances being made in our understanding of the molecular events surrounding chromosome segregation in non-mammalian and somatic cell models be considered when designing experiments for studying aneuploidy in mammalian germ cells. Accurate chromosome segregation requires the temporal control and unique interactions among a vast array of proteins and cellular organelles. Abnormal function and temporal disarray among these, and others to be identified, biochemical reactions and cellular organelles have the potential for predisposing cells to aneuploidy. Although numerous studies have demonstrated that certain chemicals (mainly those that alter microtubule function) can induce aneuploidy in mammalian germ cells, it seems relevant to point out that such data can be influenced by gender, meiotic stage, and time of cell-fixation post-treatment. Additionally, a consensus has not been reached regarding which of several germ cell aneuploidy assays most accurately reflects the human condition. More recent studies have shown that certain kinase, phosphatase, proteasome, and topoisomerase inhibitors can also induce aneuploidy in rodent germ cells. We suggest that molecular approaches be prudently incorporated into mammalian germ cell aneuploidy research in order to eventually understand the causes and mechanisms of human aneuploidy. Such an enormous undertaking would benefit from collaboration among scientists representing several disciplines.

Aneuploidy↗
PubMed1994

Determinants of Drosophila zw10 protein localization and function.

We have examined several issues concerning how the Drosophila l(1)zw10 gene product functions to ensure proper chromosome segregation. (a) We have found that in zw10 mutant embryos and larval neuroblasts, absence of the zw10 protein has no obvious effect on either the congression of chromosomes to the metaphase plate or the morphology of the metaphase spindle, although many aberrations are observed subsequently in anaphase. This suggests that activity of the zw10 protein becomes essential at anaphase onset, a time at which the zw10 protein is redistributed to the kinetochore region of the chromosomes. (b) The zw10 protein appears to bind to kinetochores in mitotically arrested cells, eventually accumulating to high levels within the chromosome mass. Our results imply that zw10 may act as part of a novel feedback pathway that normally renders sister chromatid separation dependent upon spindle integrity. (c) The localization of zw10 protein is altered by two mitotic mutations, rough deal and abnormal anaphase resolution, that specifically disrupt anaphase. These findings indicate that the zw10 protein functions as part of a multicomponent mechanism ensuring proper chromosome segregation at the beginning of anaphase.

Anaphase↗
PubMed2001

Correlation between centrosome abnormalities and chromosomal instability in human pancreatic cancer cells.

Chromosomal instability, characterized by abnormal numbers or structures of chromosomes, is a common feature of human cancers, but the mechanisms behind these changes are still unclear. Since centrosomes play a pivotal role in balanced chromosomal segregation during mitosis, we attempted to investigate the association between centrosome abnormalities and chromosomal instability in a large number of human pancreatic cancer cell lines. Immunofluorescence microscopy revealed centrosomes that were highly atypical with respect to their size, shape, and number in most cell lines. These abnormal centrosomes contributed to the assembly of multipolar spindles, resulting in defective mitosis and chromosome mis-segregation. Interestingly, a high frequency of centrosome defects inversely correlated with the growth rate of cells in culture. Fluorescence in situ hybridization revealed a dramatic variation of chromosome numbers in cell lines with the defective centrosome phenotype. Furthermore, a significant positive correlation existed between the level of centrosome defects and the level of chromosomal imbalances. These results indicate that centrosome abnormalities can lead to spindle disorganization and chromosome segregation errors, which may drive the accumulation of chromosomal alterations. Thus, defects in centrosome function may be an underlying cause of genetic instability in human pancreatic cancers.

Centrosome↗
PubMed2002

Simultaneous analysis of chromosomes and chromosome-associated proteins in mammalian oocytes and embryos.

Cytogenetic analyses of mammalian eggs and preimplantation embryos have been limited by the difficult and tedious task of preparing chromosomes from single cells or small numbers of cells. In this report we describe a new technique that is both reliable and comparatively simple. Further, since the technique does not use the conventional 3:1 methanol:acetic acid fixative, it has the advantage of producing high-resolution chromosome preparations without destroying chromosome-associated proteins. Thus, this method provides a sensitive means of conducting studies of a heretofore inaccessible period of mammalian development, and of studying proteins thought to mediate both meiotic chromosome segregation and chromatin modifications in the preimplantation embryo.

Animals↗
PubMed2024

RNAseq analysis of oocyte maturation from the germinal vesicle stage to metaphase II in pig and human.

During maturation oocytes at the germinal vesicle (GV) stage progress to metaphase II (MII). However, during in vitro maturation a proportion often fail to progress. To understand these processes, we employed RNA sequencing to examine the transcriptome profile of these three groups of oocytes from the pig. We compared our findings with similar public oocyte data from humans. The transcriptomes in oocytes that failed to progress was similar to those that did. We found in both species, the most upregulated genes in MII oocytes were associated with chromosome segregation and cell cycle processes, while the most down regulated genes were relevant to ribosomal and mitochondrial pathways. Moreover, those genes involved in chromosome segregation during GV to MII transition were conserved in pig and human. We also compared MII and GV oocyte transcriptomes at the isoform transcript level in both species. Several thousands of genes (including DTNBP1, MAPK1, RAB35, GOLGA7, ATP1A1 and ATP2B1) identified as not different in expression at a gene transcript level were found to have differences in isoform transcript levels. Many of these genes were involved in ATPase-dependent or GTPase-dependent intracellular transport in pig and human, respectively. In conclusion, our study suggests the failure to progress to MII in vitro may not be regulated at the level of the genome and that many genes are differentially regulated at the isoform level, particular those involved ATPase- or GTPase-dependent intracellular transport.

Humans↗
PubMed2000

The Saccharomyces cerevisiae centromere protein Slk19p is required for two successive divisions during meiosis.

Meiotic cell division includes two separate and distinct types of chromosome segregation. In the first segregational event the sister chromatids remain attached at the centromere; in the second the chromatids are separated. The factors that control the order of chromosome segregation during meiosis have not yet been identified but are thought to be confined to the centromere region. We showed that the centromere protein Slk19p is required for the proper execution of meiosis in Saccharomyces cerevisiae. In its absence diploid cells skip meiosis I and execute meiosis II division. Inhibiting recombination does not correct this phenotype. Surprisingly, the initiation of recombination is apparently required for meiosis II division. Thus Slk19p appears to be part of the mechanism by which the centromere controls the order of meiotic divisions.

Centromere↗
PubMed1993

Mitotic errors in somatic cells cause trisomy 21 in about 4.5% of cases and are not associated with advanced maternal age.

The study of DNA polymorphisms has permitted the determination of the parental and meiotic origin of the supernumerary chromosome 21 in families with free trisomy 21. Chromosomal segregation errors in somatic cells during mitosis were recognized after analysis of DNA markers in the pericentromeric region and (in order to identify recombination events) along the long arm of chromosome 21. Mitotic errors accounted for about 4.5% (11 of 238) of free trisomy 21 cases examined. The mean maternal age of mitotic errors was 28.5 years and there was no association with advanced maternal age. There was no preference in the parental origin of the duplicated chromosome 21. The 43 maternal meiosis II errors in this study had a mean maternal age of 34.1 years-the highest mean maternal age of all categories of chromosomal segregation errors.

Adult↗
PubMed2002

Retinoblastoma tumor suppressor and genome stability.

Retinoblastoma gene (Rb) is the prototype of tumor suppressors. Germline mutation in the retinoblastoma gene is susceptible to cancer and reintroduction of wild-type Rb is able to suppress neoplastic phenotypes. The fundamental cellular functions of Rb in the control of cell growth and differentiation are important for its tumor suppression. In general, cancer susceptibility caused by inactivation of a tumor suppressor gene results from genome instability. Accordingly, Rb may function in the maintenance of chromosome stability by influencing mitotic progression, faithful chromosome segregation, and structural remodeling of mitotic chromosomes. Rb is also implicated in the regulation of replication machinery and in the control of cell cycle checkpoints in response to DNA damage, further supporting such a role for Rb. Moreover, the mechanistic basis for Rb-mediated transcriptional repression has revealed its connection to global chromatin remodeling. It is likely that Rb suppresses tumor formation by virtue of its multiple biological activities, and a theme throughout its multiple cellular functions is its central role in controlling activities that involve chromatin remodeling. A model in which Rb controls global genome fluidity is thus proposed. Finally, a recent study provides direct evidence indicating that loss of Rb function leads to genome instability. Therefore, tumor suppressors have a common role in the maintenance of genome stability, and such a role may be pivotal for their functions in tumor suppression.

Animals↗
PubMed1993

Chromosomal rearrangement segregating with adrenoleukodystrophy: associated changes in color vision.

A patient from a large kindred with adrenoleukodystrophy showed profound disturbance of color ordering, color matching, increment thresholds, and luminosity. Except for color matching, his performance was similar to blue-cone "monochromacy," an X chromosome-linked recessive retinal dystrophy in which color vision is dichromatic, mediated by the visual pigments of rods and short-wave-sensitive cones. Color matching, however, indicated that an abnormal rudimentary visual pigment was also present. This may reflect the presence of a recombinant visual pigment protein or altered regulation of residual pigment genes, due to DNA changes--deletion of the long-wave pigment gene and reorganized sequences 5' to the pigment gene cluster--that segregate with the metabolic defect in this kindred.

Adrenoleukodystrophy↗
PubMed2004

Cell division and cell survival in the absence of survivin.

The survivin protein contains structural features of the inhibitor of apoptosis protein family. Previous studies have suggested that survivin is essential for cell survival because it counteracts an otherwise constitutive propensity to apoptosis during mitosis. In addition, survivin appears to be a component of the chromosomal passenger protein complex that participates in multiple facets of cell division. Here we report that euploid human cells do not die in the absence of survivin. Instead, depletion of survivin caused defects in cell division, followed by an arrest of DNA synthesis due to activation of a checkpoint involving the tumor suppressor protein p53. During anaphase mitosis in survivin-deficient cells, sister chromatids disjoined normally, but one or more of the sister chromatids frequently lagged behind the main mass of segregating chromosomes, probably because of merotelic kinetochore attachments. Survivin-deficient cells initiated but failed to complete cytokinesis, apparently because the spindle midzone and midbody microtublues were absent during late mitosis. The abnormalities of both chromosome segregation and cytokinesis could be attributed to a defect in the chromosomal passenger protein complex, with a consequent mislocalization of the kinesin-like motor protein MKLP-1 playing a more immediate role in the microtubule abnormalities. Depletion of another chromosomal passenger protein, aurora-B, recapitulated the survivin RNA interference phenotypes. We conclude that survivin can be essential for the proliferation of normal human cells by virtue of its contributions to accurate sister chromatid segregation and assembly/stabilization of microtubules in late mitosis. However, the protein is not inevitably required for the survival of normal cells.

Cell Division↗
PubMed2004

Nek2A kinase regulates the localization of numatrin to centrosome in mitosis.

Chromosome segregation in mitosis is orchestrated by the kinetochore and spindle microtubules stemming from two centrosomes. Our recent studies demonstrated the importance of Nek2A in faithful chromosome segregation during mitosis. Here, we report that Nek2A regulates the function of numatrin in mitosis. The biochemical interaction between Nek2A and numatrin in mitotic cells was revealed by a set of reciprocal immunoprecipitation experiments using Nek2A and numatrin antibodies, respectively. The interaction is validated by a pull-down assay using recombinant Nek2A and numatrin proteins. Moreover, our immunofluorescence studies demonstrate that numatrin becomes centrosome-associated as the cell enters into mitosis and depart from the centrosome after sister chromatid separation in anaphase. The co-localization of numatrin and Nek2A to the centrosome suggests their interaction with and involvement in centrosome function. Indeed, elimination of Nek2A kinase by siRNA diminished its association with the centrosome. Furthermore, we show that numatrin is phosphorylated by wild type but not kinase-death Nek2A. Our studies suggest that the Nek2A kinase cascade is essential for the localization of numatrin to the centrosome.

Centrosome↗
PubMed2002

The segregation of the Escherichia coli origin and terminus of replication.

Escherichia coli chromosome replication forks are tethered to the cell centre. Two opposing models describe how the chromosomes segregate. In the extrusion-capture model, newly replicated DNA is fed bi-directionally from the forks toward the cell poles, forming new chromosomes in each cell half. Starting with the origins, chromosomal regions segregate away from their sisters progressively as they are replicated. The termini segregate last. In the sister chromosome cohesion model, replication produces sister chromosomes that are paired along much of their length. The origins and most other chromosomal regions remain paired until late in the replication cycle, and all segregate together. We use a combination of microscopy and flow cytometry to determine the relationship of origin and terminus segregation to the cell cycle. Origin segregation frequently follows closely after initiation, in strong support of the extrusion-capture model. The spatial disposition of the origin and terminus sequences also fits this model. Terminus segregation occurs extremely late in the cell cycle as the daughter cells separate. As the septum begins to invaginate, the termini of the completed sister chromosomes are transiently held apart at the cell centre, on opposite sides of the cell. This may facilitate the resolution of topological linkages between the chromosomes.

Base Sequence↗