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 991 records · Page 55Linked to original sources
PubMed2001

HIM-10 is required for kinetochore structure and function on Caenorhabditis elegans holocentric chromosomes.

Macromolecular structures called kinetochores attach and move chromosomes within the spindle during chromosome segregation. Using electron microscopy, we identified a structure on the holocentric mitotic and meiotic chromosomes of Caenorhabditis elegans that resembles the mammalian kinetochore. This structure faces the poles on mitotic chromosomes but encircles meiotic chromosomes. Worm kinetochores require the evolutionarily conserved HIM-10 protein for their structure and function. HIM-10 localizes to the kinetochores and mediates attachment of chromosomes to the spindle. Depletion of HIM-10 disrupts kinetochore structure, causes a failure of bipolar spindle attachment, and results in chromosome nondisjunction. HIM-10 is related to the Nuf2 kinetochore proteins conserved from yeast to humans. Thus, the extended kinetochores characteristic of C. elegans holocentric chromosomes provide a guide to the structure, molecular architecture, and function of conventional kinetochores.

Animals↗
PubMed1984

Cytogenetic analysis of a segment of the Y chromosome of Drosophila melanogaster.

Males carrying a large deficiency in the long arm of the Y chromosome known to delete the fertility gene kl-2 are sterile and exhibit a complex phenotype: (1) First metaphase chromosomes are irregular in outline and appear sticky; (2) spermatids contain micronuclei; (3) the nebenkerns of the spermatids are nonuniform in size; (4) a high molecular weight protein ordinarily present in sperm is absent; and (5) crystals appear in the nucleus and cytoplasm of spermatocytes and spermatids. In such males that carry Ste+ on their X chromosome the crystals appear long and needle shaped; in Ste males the needles are much shorter and assemble into star-shaped aggregates. The large deficiency may be subdivided into two shorter component deficiencies. The more distal is male sterile and lacks the high molecular weight polypeptide; the more proximal is responsible for the remainder of the phenotype. Ste males carrying the more proximal component deficiency are sterile, but Ste+ males are fertile. Genetic studies of chromosome segregation in such males reveal that (1) both the sex chromosomes and the large autosomes undergo nondisjunction, (2) the fourth chromosomes disjoin regularly, (3) sex chromosome nondisjunction is more frequent in cells in which the second or third chromosomes nondisjoin than in cells in which autosomal disjunction is regular, (4) in doubly exceptional cells, the sex chromosomes tend to segregate to the opposite pole from the autosomes and (5) there is meiotic drive; i.e., reciprocal meiotic products are not recovered with equal frequencies, complements with fewer chromosomes being recovered more frequently than those with more chromosomes. The proximal component deficiency can itself be further subdivided into two smaller component deficiencies, both of which have nearly normal spermatogenic phenotypes as observed in the light microscope. Meiosis in Ste+ males carrying either of these small Y deficiencies is normal; Ste males, however, exhibit low levels of sex chromosome nondisjunction with either deficient Y. The meiotic phenotype is apparently sensitive to the amount of Y chromosome missing and to the Ste constitution of the X chromosome.

Animals↗
PubMed1983

Further evidence for a polymorphism in gametic segregation in the tetraploid treefrog Hyla versicolor using a glutamate oxaloacetic transaminase locus.

Intra- and interspecific cross combinations between the tetraploid treefrog Hyla versicolor, and between H. versicolor and the diploid treefrog Hyla chrysoscelis were performed. Progeny phenotypes resulting from these crosses were examined electrophoretically using a polymorphic glutamate oxaloacetic transaminase (GOT-1) locus, to determine the mechanism of chromosome segregation in H. versicolor, and to test theoretical expectations for isozyme expression in interspecific (2n X 4n or 4n X 2n) hybrids. In some intraspecific tetraploid crosses progeny phenotypes fit a disomic mode of segregation, whereas in other crosses a tetrasomic mode of segregation was the most probable. Additional crosses produced phenotypic ratios that conformed to either a disomic or tetrasomic mode of segregation. These results suggest that a polymorphism, with respect to segregation of gametes, exists in H. versicolor, resulting from differences in chromosome pairings during meiosis I. This polymorphism in gametic segregation occurred in both sexes. Certain crosses, however, produced phenotypic ratios that did not conform to any chromosome segregation model. Progeny phenotypes observed from most interspecific crosses conformed to expected interspecific isozyme staining intensity models. Symmetrical heterozygotes, representing either a single dose for both alternate alleles or double doses for both alternate alleles, were also observed. Such phenotypes are unexpected in triploid progeny. A null allele was postulated to account for the aberrant segregation ratios and phenotypes observed in certain intra- and interspecific crosses.

Animals↗
PubMed2004

Spo13 facilitates monopolin recruitment to kinetochores and regulates maintenance of centromeric cohesion during yeast meiosis.

BACKGROUND: Cells undergoing meiosis perform two consecutive divisions after a single round of DNA replication. During the first meiotic division, homologous chromosomes segregate to opposite poles. This is achieved by (1) the pairing of maternal and paternal chromosomes via recombination producing chiasmata, (2) coorientation of homologous chromosomes such that sister chromatids attach to the same spindle pole, and (3) resolution of chiasmata by proteolytic cleavage by separase of the meiotic-specific cohesin Rec8 along chromosome arms. Crucially, cohesin at centromeres is retained to allow sister centromeres to biorient at the second division. Little is known about how these meiosis I-specific events are regulated. RESULTS: Here, we show that Spo13, a centromere-associated protein produced exclusively during meiosis I, is required to prevent sister kinetochore biorientation by facilitating the recruitment of the monopolin complex to kinetochores. Spo13 is also required for the reaccumulation of securin, the persistence of centromeric cohesin during meiosis II, and the maintenance of a metaphase I arrest induced by downregulation of the APC/C activator CDC20. CONCLUSION: Spo13 is a key regulator of several meiosis I events. The presence of Spo13 at centromere-surrounding regions is consistent with the notion that it plays a direct role in both monopolin recruitment to centromeres during meiosis I and maintenance of centromeric cohesion between the meiotic divisions. Spo13 may also limit separase activity after the first division by ensuring securin reaccumulation and, in doing so, preventing precocious removal from chromatin of centromeric cohesin.

ATP-Binding Cassette Transporters↗
PubMed2002

C. elegans condensin promotes mitotic chromosome architecture, centromere organization, and sister chromatid segregation during mitosis and meiosis.

Chromosome segregation and X-chromosome gene regulation in Caenorhabditis elegans share the component MIX-1, a mitotic protein that also represses X-linked genes during dosage compensation. MIX-1 achieves its dual roles through interactions with different protein partners. To repress gene expression, MIX-1 acts in an X-chromosome complex that resembles the mitotic condensin complex yet lacks chromosome segregation function. Here we show that MIX-1 interacts with a mitotic condensin subunit, SMC-4, to achieve chromosome segregation. The SMC-4/MIX-1 complex positively supercoils DNA in vitro and is required for mitotic chromosome structure and segregation in vivo. Thus, C. elegans has two condensin complexes, one conserved for mitosis and another specialized for gene regulation. SMC-4 and MIX-1 colocalize with centromere proteins on condensed mitotic chromosomes and are required for the restricted orientation of centromeres toward spindle poles. This cell cycle-dependent localization requires AIR-2/AuroraB kinase. Depletion of SMC-4/MIX-1 causes aberrant mitotic chromosome structure and segregation, but not dramatic decondensation at metaphase. Moreover, SMC-4/MIX-1 depletion disrupts sister chromatid segregation during meiosis II but not homologous chromosome segregation during meiosis I, although both processes require chromosome condensation. These results imply that condensin is not simply required for compaction, but plays a more complex role in chromosome architecture that is essential for mitotic and meiotic sister chromatid segregation.

Adenosine Triphosphatases↗
PubMed2005

Towards understanding the molecular basis of bacterial DNA segregation.

Bacteria ensure the fidelity of genetic inheritance by the coordinated control of chromosome segregation and cell division. Here, we review the molecules and mechanisms that govern the correct subcellular positioning and rapid separation of newly replicated chromosomes and plasmids towards the cell poles and, significantly, the emergence of mitotic-like machineries capable of segregating plasmid DNA. We further describe surprising similarities between proteins involved in DNA partitioning (ParA/ParB) and control of cell division (MinD/MinE), suggesting a mechanism for intracellular positioning common to the two processes. Finally, we discuss the role that the bacterial cytoskeleton plays in DNA partitioning and the missing link between prokaryotes and eukaryotes that is bacterial mechano-chemical motor proteins.

Bacterial Physiological Phenomena↗
PubMed2004

Cell cycle regulation of central spindle assembly.

The bipolar mitotic spindle is responsible for segregating sister chromatids at anaphase. Microtubule motor proteins generate spindle bipolarity and enable the spindle to perform mechanical work. A major change in spindle architecture occurs at anaphase onset when central spindle assembly begins. This structure regulates the initiation of cytokinesis and is essential for its completion. Central spindle assembly requires the centralspindlin complex composed of the Caenorhabditis elegans ZEN-4 (mammalian orthologue MKLP1) kinesin-like protein and the Rho family GAP CYK-4 (MgcRacGAP). Here we describe a regulatory mechanism that controls the timing of central spindle assembly. The mitotic kinase Cdk1/cyclin B phosphorylates the motor domain of ZEN-4 on a conserved site within a basic amino-terminal extension characteristic of the MKLP1 subfamily. Phosphorylation by Cdk1 diminishes the motor activity of ZEN-4 by reducing its affinity for microtubules. Preventing Cdk1 phosphorylation of ZEN-4/MKLP1 causes enhanced metaphase spindle localization and defects in chromosome segregation. Thus, phosphoregulation of the motor domain of MKLP1 kinesin ensures that central spindle assembly occurs at the appropriate time in the cell cycle and maintains genomic stability.

Adenosine Triphosphatases↗
PubMed1978

Genetic studies on heterochromatin in Drosophila melanogaster and their implications for the functions of satellite DNA.

In Drosophila melanogaster the centromeric heterochromatin of all chromosomes consists almost entirely of several different satellite DNA sequences. In view of this we have examined by genetic means the meiotic consequences of X chromosomes with partial deletions of their heterochromatin, and have found that the amount and position of recombination on each heterochromatically deleted X is substantially different from that of a normal X. It appears that the amount of heterochromatin is important in modifying the "centromere effect" on recombination.--In all the deleted Xs tested, chromosome segregation is not appreciably altered from that of a nondeleted control chromosome. Thus satellite DNA does not appear to be an important factor in determining the regular segregation of sex chromosomes in Drosophila. Additionally, since X chromosomes with massive satellite DNA deficiencies are able to participate in a chromocenter within salivary gland nuclei, a major role of satellite DNA in chromocenter formation in this tissue is also quite unlikely.--In order to examine the mechanisms by which the amount of satellite DNA is increased or decreased in vivo, we have measured cytologically the frequency of spontaneous sister chromatid exchanges in a ring Y chromosome which is entirely heterochromatic and consists almost exclusively of satellite DNA. In larval neuroblast cells the frequency of spontaneous SCE in this Y is approximately 0.3% per cell division. Since there is no meiotic recombination in D. melanogaster males and since meiotic recombination in the female does not occur in heterochromatin, our results provide a minimum estimate of the in vivo frequency of SCE in C-banded heterochromatin (which is predominantly simple sequence DNA), without the usual complications of substituted base analogs, incorporated radioactive label or substantial genetic content.--We emphasise that: (a) satellite DNA is not implicated in any major way in recognition processes such as meiotic homologue recognition or chromocenter formation in salivaries, (b) there is likely to be continuous variation in the amount of satellite DNA between individuals of a species; and (c) the amount of satellite DNA can have a crucial functional role in the meiotic recombination system.

Animals↗
PubMed2003

AHP2 is required for bivalent formation and for segregation of homologous chromosomes in Arabidopsis meiosis.

A new Arabidopsis meiotic mutant has been isolated. Homozygous ahp2-1 (Arabidopsis homologue pairing 2) plants were sterile because of failure of both male and female gametophyte development. Fluorescent in situ hybridisation showed that in ahp2-1 male meiocytes, chromosomes did not form bivalents during prophase I and instead seemed to associate indiscriminately. Chromosome fragmentation, chromatin bridges and unbalanced segregation were seen in anaphase I and anaphase II. The ahp2-1 mutation was caused by a T-DNA insertion in an Arabidopsis homologue of meu13+, which has been implicated in homologous chromosome pairing during meiosis in Schizosaccharomyces pombe. Our results suggest that meu13+ function is conserved in higher eukaryotes and support the idea that Arabidopsis, yeast and mouse share a pairing pathway that is not present in Drosophila melanogaster and Caenorhabditis elegans.

Amino Acid Sequence↗
PubMed2003

A deficiency screen of the major autosomes identifies a gene (matrimony) that is haplo-insufficient for achiasmate segregation in Drosophila oocytes.

In Drosophila oocytes, euchromatic homolog-homolog associations are released at the end of pachytene, while heterochromatic pairings persist until metaphase I. A screen of 123 autosomal deficiencies for dominant effects on achiasmate chromosome segregation has identified a single gene that is haplo-insufficient for homologous achiasmate segregation and whose product may be required for the maintenance of such heterochromatic pairings. Of the deficiencies tested, only one exhibited a strong dominant effect on achiasmate segregation, inducing both X and fourth chromosome nondisjunction in FM7/X females. Five overlapping deficiencies showed a similar dominant effect on achiasmate chromosome disjunction and mapped the haplo-insufficient meiotic gene to a small interval within 66C7-12. A P-element insertion mutation in this interval exhibits a similar dominant effect on achiasmate segregation, inducing both high levels of X and fourth chromosome nondisjunction in FM7/X females and high levels of fourth chromosome nondisjunction in X/X females. The insertion site for this P element lies immediately upstream of CG18543, and germline expression of a UAS-CG18543 cDNA construct driven by nanos-GAL4 fully rescues the dominant meiotic defect. We conclude that CG18543 is the haplo-insufficient gene and have renamed this gene matrimony (mtrm). Cytological studies of prometaphase and metaphase I in mtrm hemizygotes demonstrate that achiasmate chromosomes are not properly positioned with respect to their homolog on the meiotic spindle. One possible, albeit speculative, interpretation of these data is that the presence of only a single copy of mtrm disrupts the function of whatever "glue" holds heterochromatically paired homologs together from the end of pachytene until metaphase I.

Animals↗
PubMed2003

Mutation load, functional overlap, and synthetic lethality in the evolution and treatment of cancer.

The efficacy of conventional anti-cancer drugs is puzzling in view of the ubiquitous tissue distribution and vital nature of their targets. Differences in cell cycling rates are not thought sufficient to explain chemotherapeutic selectivity. I suggest an alternative possibility based on the combinatorial effects of mutations in cancer cells. This model incorporates the concepts of synthetic-lethal interactions and mutation loads to explain the drug sensitivity of cancer cells. From this perspective, drugs that target complex processes that utilize genetically redundant or overlapping components, such as DNA replication and chromosome segregation, offer attractive target opportunities.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Increased missegregation and chromosome loss with decreasing chromosome size in vertebrate cells.

Chromosome engineering has allowed the generation of an extensive and well-defined series of linear human X centromere-based minichromosomes, which has been used to investigate the influence of size and structure on chromosome segregation in vertebrate cells. A clear relationship between overall chromosome size and mitotic stability was detected, with decreasing size associated with increasing loss rates. In chicken DT40, the lower size limit for prolonged mitotic stability is approximately 550 kb: at 450 kb, there was a dramatic increase in chromosome loss, while structures of approximately 200 kb could not be recovered. In human HT1080 cells, the size threshold for mitotic stability is approximately 1.6 Mb. Minichromosomes of 0.55-1.0 Mb can be recovered, but display high loss rates. However, all minichromosomes examined exhibited more segregation errors than normal chromosomes in HT1080 cells. This error rate increases with decreased size and correlates with reduced levels of CENP-A and Aurora B. In mouse LA-9 and Indian muntjac FM7 cells, the size requirements for mitotic stability are much greater. In mouse, a human 2.7-Mb minichromosome is rarely able to propagate a kinetochore and behaves acentrically. In Indian muntjac, CENP-C associates with the human minichromosome, but the mitotic apparatus appears unable to handle its segregation.

Animals↗
PubMed2001

Evolutionary conservation between budding yeast and human kinetochores.

Accurate chromosome segregation during mitosis requires the correct assembly of kinetochores--complexes of centromeric DNA and proteins that link chromosomes to spindle microtubules. Studies on the kinetochore of the budding yeast Saccharomyces cerevisiae have revealed functionally novel components of the kinetochore and its regulatory complexes, some of which are highly conserved in humans.

Chromosome Segregation↗
PubMed1995

Exit from mitosis is regulated by Drosophila fizzy and the sequential destruction of cyclins A, B and B3.

While entry into mitosis is triggered by activation of cdc2 kinase, exit from mitosis requires inactivation of this kinase. Inactivation results from proteolytic degradation of the regulatory cyclin subunits during mitosis. At least three different cyclin types, cyclins A, B and B3, associate with cdc2 kinase in higher eukaryotes and are sequentially degraded in mitosis. We show here that mutations in the Drosophila gene fizzy (fzy) block the mitotic degradation of these cyclins. Moreover, expression of mutant cyclins (delta cyclins) lacking the destruction box motif required for mitotic degradation affects mitotic progression at distinct stages. Deltacyclin A results in a delay in metaphase, deltacyclin B in an early anaphase arrest and deltacyclin B3 in a late anaphase arrest, suggesting that mitotic progression beyond metaphase is ordered by the sequential degradation of these different cyclins. Coexpression of deltacyclins A, B and B3 allows a delayed separation of sister chromosomes, but interferes wit chromosome segregation to the poles. Mutations in fzy block both sister chromosome separation and segregation, indicating that fzy plays a crucial role in the metaphase/anaphase transition.

Anaphase↗
PubMed2006

Comment on "Cell type regulates selective segregation of mouse chromosome 7 DNA strands in mitosis".

Armakolas and Klar (Reports, 24 February 2006, p. 1146) suggested that segregation of mouse chromosome 7, after induction of a site-specific crossover between homologous chromosomes, is driven by a preferential inheritance of the old Watson and the old Crick DNA strands. However, this interpretation only considered half of the possible outcomes. The conjecture fails when all possible outcomes are examined.

Animals↗
PubMed2002

Aberrations of centrosomes in adrenocortical tumors.

The frequent and generalized chromosomal imbalances that are characteristic of adrenocortical carcinomas suggest that incomplete chromosome segregation often takes place in these tumors. As a step towards elucidating the mechanism behind the multiple numerical chromosomal aberrations, we have evaluated a series of 14 such tumors for centrosome abnormalities using immunohistochemical detection of the gamma-tubulin centrosome component. The proportion of cells with more than the expected number of 2 centrosomes was moderately increased in the 4 adenomas (1-7%), while a high increase was observed in the 10 carcinomas (1-19%), as compared to the normal reference tissues (0.3%) (p<0.001). Similarly, the centrosome amplification tended to be more pronounced in the carcinomas where the aberrant cells carried 3 or 4 positive signals in 9 of the 10 tumors, and 6 signals were recorded in one tumor, while in the adenomas more than 3 signals was only recorded in one of the 4 cases. The findings demonstrate that centrosome amplifications occur frequently in both adrenocortical adenomas and carcinomas, thus supporting its role in driving the tumor development as opposed to being a consequence of it. Furthermore, the more pronounced occurrence in the malignant form as well as in the larger tumors, offers one likely explanation for the increasing generalized aneuploidy observed during the tumor development, and points to new therapeutic strategies aimed at restoring normal centrosome function.

Adenoma↗
PubMed2002

Cosegregation of chromosomes containing immortal DNA strands in cells that cycle with asymmetric stem cell kinetics.

A long-standing intriguing hypothesis in cancer biology is that adult stem cells avoid mutations from DNA replication errors by a unique pattern of chromosome segregation. At each asymmetric cell division, adult stem cells have been postulated to selectively retain a set of chromosomes that contain old template DNA strands (i.e., "immortal DNA strands"). Using cultured cells that cycle with asymmetric cell kinetics, we confirmed both the existence of immortal DNA strands and the cosegregation of chromosomes that bear them. Our findings also lead us to propose a role for immortal DNA strands in tissue aging as well as cancer.

Adult↗
PubMed1998

A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos.

S. cerevisiae Ipl1, Drosophila Aurora, and the mammalian centrosomal protein IAK-1 define a new subfamily of serine/threonine kinases that regulate chromosome segregation and mitotic spindle dynamics. Mutations in ipl1 and aurora result in the generation of severely aneuploid cells and, in the case of aurora, monopolar spindles arising from a failure in centrosome separation. Here we show that a related, essential protein from C. elegans, AIR-1 (Aurora/Ipl1 related), is localized to mitotic centrosomes. Disruption of AIR-1 protein expression in C. elegans embryos results in severe aneuploidy and embryonic lethality. Unlike aurora mutants, this aneuploidy does not arise from a failure in centrosome separation. Bipolar spindles are formed in the absence of AIR-1, but they appear to be disorganized and are nucleated by abnormal-looking centrosomes. In addition to its requirement during mitosis, AIR-1 may regulate microtubule-based developmental processes as well. Our data suggests AIR-1 plays a role in P-granule segregation and the association of the germline factor PIE-1 with centrosomes.

Amino Acid Sequence↗