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Results for “Chromosome Segregation”

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PubMed2004

Schizosaccharomyces pombe RanGAP homolog, SpRna1, is required for centromeric silencing and chromosome segregation.

We isolated 11 independent temperature-sensitive (ts) mutants of Schizosaccharomyces pombe RanGAP, SpRna1 that have several amino acid changes in the conserved domains of RanGAP. Resulting Sprna1ts showed a strong defect in mitotic chromosome segregation, but did not in nucleocytoplasmic transport and microtubule formation. In addition to Sprna1+ and Spksp1+, the clr4+ (histone H3-K9 methyltransferase), the S. pombe gene, SPAC25A8.01c, designated snf2SR+ (a member of the chromatin remodeling factors, Snf2 family with DNA-dependent ATPase activity), but not the spi1+ (S. pombe Ran homolog), rescued a lethality of Sprna1ts. Both Clr4 and Snf2 were reported to be involved in heterochromatin formation essential for building the centromeres. Consistently, Sprna1ts was defective in gene-silencing at the centromeres. But a silencing at the telomere, another heterochromatic region, was normal in all of Sprna1ts strains, indicating SpRna1 in general did not function for a heterochromatin formation. snf2SR+ rescued a centromeric silencing defect and Deltaclr4+ was synthetic lethal with Sprna1ts. Taken together, SpRna1 was suggested to function for constructing the centromeres, by cooperating with Clr4 and Snf2SR. Loss of SpRna1 activity, therefore, caused chromosome missegregation.

Active Transport, Cell Nucleus↗

PubMed2005

Chromosome segregation: Aurora B gets Tousled.

Aurora B kinases play important roles during mitosis in eukaryotic cells; new work in Caenorhabditis elegans has identified the Tousled kinase TLK-1 as a substrate activator of the model nematode's Aurora B kinase AIR-2 which acts to ensure proper chromosome segregation during cell division.

Animals↗

PubMed1993

Chromosome segregation in yeast.

Because of their genetic tractability, much has been learned concerning the mechanisms of chromosome segregation in budding yeast, Saccharomyces cerevisiae, and fission yeast, Schizosaccharomyces pombe. This chapter reviews the cytology and molecular and cell biology of mitosis in both of these yeasts. Current knowledge about the components of the mitotic spindle apparatus, including spindle pole bodies, centromeres, and microtubule components and motors, is summarized. Mechanisms of mitosis such as establishment and positioning of the mitotic spindle apparatus, anaphase A, and anaphase B are reviewed.

Cell Cycle↗

PubMed1990

A kinesin-like protein required for distributive chromosome segregation in Drosophila.

The nod gene is required for the distributive segregation of nonexchange chromosomes during meiosis in D. melanogaster. Loss-of-function nod mutations cause nondisjunction and loss of nonrecombinant chromosomes both at meiosis I and during subsequent mitotic divisions. We have cloned the nod locus, examined its expression patterns, and determined its coding sequence. In adults the nod transcript is only present in females, consistent with the observation that males do not use the distributive segregation system. However, the nod locus is also transcribed in the embryonic, larval, and pupal stages of development, and possibly in all dividing cells. Finally, the N-terminal domain of the predicted nod protein has amino acid similarity to the mechanochemical domain of kinesin heavy chain; however, the C-terminal domain is unlike that of kinesin heavy chain or of any previously reported protein. Thus, the nod protein is a member of the kinesin superfamily and may be a microtubule motor.

Adenosine Triphosphatases↗

PubMed1992

The Drosophila l(1)zw10 gene product, required for accurate mitotic chromosome segregation, is redistributed at anaphase onset.

Mutations in the gene l(1)zw10 disrupt the accuracy of chromosome segregation in a variety of cell types during the course of Drosophila development. Cytological analysis of mutant larval brain neuroblasts shows very high levels of aneuploid cells. Many anaphase figures are aberrant, the most frequent abnormality being the presence of lagging chromosomes that remain in the vicinity of the metaphase plate when the other chromosomes have migrated toward the spindle poles. Finally, the centromeric connection between sister chromatids in mutant neuroblasts treated with colchicine often appears to be broken, in contrast with similarly treated control neuroblasts. The 85-kD protein encoded by the l(1)zw10 locus displays a dynamic pattern of localization in the course of the embryonic cell cycle. It is excluded from the nuclei during interphase, but migrates into the nuclear zone during prometaphase. At metaphase, the zw10 antigen is found in a novel filamentous structure that may be specifically associated with kinetochore microtubules. Upon anaphase onset, there is an extremely rapid redistribution of the zw10 protein to a location at or near the kinetochores of the separating chromosomes.

Amino Acid Sequence↗

PubMed2006

The human kinetochore proteins Nnf1R and Mcm21R are required for accurate chromosome segregation.

Kinetochores (KTs) assemble on centromeric DNA, bi-orient paired sister chromatids on spindle microtubules (MTs) and control cell-cycle progression via the spindle assembly checkpoint. Genetic and biochemical studies in budding yeast have established that three 'linker' complexes, MIND, COMA and NDC80, play essential but distinct roles in KT assembly and chromosome segregation. To determine whether similar linker activities are present at human KTs, we have compared the functions of Nnf1R and Mcm21R, recently identified MIND and COMA subunits, and Nuf2R, a well-characterized NDC80 subunit. We find that the three proteins bind to KTs independent of each other and with distinct cell-cycle profiles. MT-KT attachment is aberrant in Nnf1R- and Mcm21R-depleted cells, whereas it is lost in the absence of Nuf2R. Defective attachments in Nnf1R-depleted cells prevent chromosome congression, whereas those in Mcm21R-depleted cells interfere with spindle assembly. All three human KT proteins are necessary for correct binding of spindle checkpoint proteins to KTs. The differing functions and KT-binding properties of Nnf1R, Mcm21R and Nuf2R suggest that, like their yeast counterparts, the proteins act independent of each other in KT assembly, but that their combined activities are required for checkpoint signaling.

Cell Cycle Proteins↗

PubMed1996

Morewright (mwr), a new meiotic mutant of Drosophila melanogaster affecting nonexchange chromosome segregation.

A new meiotic mutation, morewright (mwr) was identified by screening for new mutations that act as dominant enhancers of the dosage-sensitive Drosophila melanogaster female meiotic mutant, nodDTW.mwr is a recessive meiotic mutant, specifically impairing the segregation of nonexchange chromosomes. Cytological evidence suggests that the meiotic defect in mwr/mwr females is in homologue recognition because the chromosomes appear to be misaligned on an intact spindle. The mwr mutation was recovered during a screen of random P-element insertions on a chromosome with a single insertion located at 50C. The P-element insertion is a recessive female-sterile mutation. While excision of the P element from the mwr-bearing chromosome partially relieves the female sterility, the excisions retain the dominant nodDTW-enhancing activity. The mwr meiotic phenotype maps very close to the female-sterile P insertion. Thus the mwr locus appears to encode a function required for partner recognition in meiosis, although its relationship to the neighboring female-sterile mutation remains to be elucidated.

Animals↗

PubMed1991

Escherichia coli XerC recombinase is required for chromosomal segregation at cell division.

XerC is a site-specific recombinase of the bacteriophage lambda integrase family that is encoded by xerC at 3700 kbp on the genetic map of Escherichia coli. The protein was originally identified through its role in converting multimers of plasmid ColE1 to monomers; only monomers are stably inherited. Here we demonstrate that XerC also has a role in the segregation of replicated chromosomes at cell division. xerC mutants form filaments with aberrant nucleotides that appear unable to partition correctly. A DNA segment (dif) from the replication terminus region of the E. coli chromosome binds XerC and acts as a substrate for XerC-mediated site-specific recombination when inserted into multicopy plasmids. This dif segment contains a region of 28 bp with sequence similarity to the crossover region of ColE1 cer. The cell division phenotype of xerC mutants is suppressed in strains deficient in homologous recombination, suggesting that the role of XerC/dif in chromosomal metabolism is to convert any chromosomal multimers (arising through homologous recombination) to monomers.

Aminopeptidases↗

PubMed2002

Nnf1p, Dsn1p, Mtw1p, and Nsl1p: a new group of proteins important for chromosome segregation in Saccharomyces cerevisiae.

Previously, antibodies were raised against a nuclear envelope-enriched fraction of yeast, and the essential gene NNF1 was cloned by reverse genetics. Here it is shown that the conditional nnf1-17 mutant has decreased stability of a minichromosome in addition to mitotic spindle defects. I have identified the novel essential genes DSN1, DSN3, and NSL1 through genetic interactions with nnf1-17. Dsn3p was found to be equivalent to the kinetochore protein Mtw1p. By indirect immunofluorescence, all four proteins, Nnf1p, Mtw1p, Dsn1p, and Nsl1p, colocalize and are found in the region of the spindle poles. Based on the colocalization of these four proteins, the minichromosome instability and the spindle defects seen in nnf1 mutants, I propose that Nnf1p is part of a new group of proteins necessary for chromosome segregation.

Alleles↗

PubMed1995

Sequence similarities between the yeast chromosome segregation protein Mif2 and the mammalian centromere protein CENP-C.

A short stretch of strong homology between the Saccharomyces cerevisiae chromosome segregation protein Mif2 and the DNA-binding motifs of the Drosophila D1 and mammalian HMGI(Y) chromosomal proteins suggested that Mif2 may act directly on chromosomes. Because this conserved motif is involved in binding A.T DNA, it was proposed that Mif2 may interact with chromosomes at the highly A + T-rich DNA element found in yeast centromeres. Comparison of the Mif2 amino-acid sequence with sequence databases showed that Mif2 shares at least two regions of similarity with the mammalian centromere protein CENP-C, suggesting an evolutionary conservation of centromere protein function from yeast to mammals. The order, spacing and location of these regions are also similar in the two proteins. Sequence analysis of several conditional lethal alleles of MIF2 generated by random mutagenesis revealed mutations in regions homologous to CENP-C, as well as in the highly conserved A.T DNA-binding motif. A potential phosphorylation site for p34cdc2 kinase located adjacent to the A.T DNA-binding motif was also found to be mutated in one of the mutants, suggesting that phosphorylation at this site may be important for Mif2 function and possibly for DNA binding.

Amino Acid Sequence↗

PubMedDate not supplied

Possible function of the cytoplasmic axial filaments in chromosomal segregation and cellular division of Escherichia coli.

Expression of the cafA gene at 71 min on the E. coli chromosome map by use of a high copy number expression vector caused (1) overproduction of the 51 kDa CafA protein, (2) formation of chains of normal cells and shorter anucleate cells, and (3) formation of flexible, tough structures, which we call 'cytoplasmic axial filaments', running throughout the centre of the chained cells. In this article we shall describe the morphology, physiology and possible functions of the cytoplasmic axial filament structure. This structure could be a strong candidate for one of the procaryotic cytoskeletal/cytokinetic elements functioning in cellular extension and division, chromosomal segregation and other important mechanisms involved in the proliferation of procaryotic cells.

Amino Acid Sequence↗

PubMed1983

X chromosome-induced reversion of chromosome segregation in mouse/Chinese hamster somatic cell hybrids. Cellular recognition of native and foreign X chromosomes.

The direction of chromosome loss in two sets of mouse-Chinese hamster hybrids was compared with the direction of segregation of the same hybrids, to which an additional X chromosome derived from either of the mouse sarcoma lines MethAa, MethAs, or CMS4, was introduced at the time of the fusion. The addition of the X chromosome was carried out by substituting in place of the Chinese hamster parent a mouse X containing microcell hybrid of the latter. It was found that the addition of an X chromosome reverses the direction of chromosome segregation, but it can do so only if the mouse parent in the hybridization is different from the line from which the X originated. The possible reasons for recognition by the cells of a native and a foreign X are discussed. The existence of a multigene family on the X chromosome, involved in this recognition, is proposed.

Animals↗

PubMed1998

Depletion of a Drosophila homolog of yeast Sup35p disrupts spindle assembly, chromosome segregation, and cytokinesis during male meiosis.

In the course of a genetic screen for male-sterile mutations in Drosophila affecting chromosome segregation during the meiotic divisions in spermatocytes, we identified the mutation dsup35(63D). Examination of mutant testes showed that chromosome misbehavior was a consequence of major disruptions in meiotic spindle assembly. These perturbations included problems in aster formation, separation, and migration around the nuclear envelope; aberrations in spindle organization and integrity; and disappearance of the ana/telophase central spindle, which in turn disrupts cytokinesis. The dsup35(63D) mutation is caused by a P element insertion that affects, specifically in the testis, the expression of a gene (dsup35) encoding the Drosophila homolog of the yeast Sup35p and Xenopus eRF3 proteins. These proteins are involved in the termination of polypeptide synthesis on ribosomes, but previous studies have suggested that Sup35p and closely related proteins of the same family also interact directly with microtubules. An affinity-purified antibody directed against the product of the dsup35 gene was prepared; interestingly, this antibody specifically labels primary spermatocytes in one or two discrete foci of unknown structure within the nucleoplasm. We discuss how depletion of the dsup35 gene product in spermatocytes might lead to the global disruptions in meiotic spindle assembly seen in mutant spermatocytes.

Amino Acid Sequence↗

PubMed1989

Expression and DNA sequence of RED1, a gene required for meiosis I chromosome segregation in yeast.

Genetic studies have previously demonstrated that the RED1 gene of Saccharomyces cerevisiae is required for chromosome segregation at the first meiotic division. Northern blot hybridization analysis indicates that the RED1 gene produces two transcripts of 2.75 and 3.2 kilobases. The major 2.75 kb transcript is not present in mitotic cells and is meiotically induced to accumulate maximally just prior to the meiosis I division. The DNA sequence of the RED1 gene was determined and used to predict the amino acid sequence of the encoded gene product. The RED1 protein is 827 amino acids in length and has a molecular weight of 95.5 kilodaltons. There is no significant homology between the RED1 amino acid sequence and other known protein sequences, including those encoded by genes essential for meiosis.

Amino Acid Sequence↗

PubMed2006

The Forkhead transcription factor Hcm1 regulates chromosome segregation genes and fills the S-phase gap in the transcriptional circuitry of the cell cycle.

Transcription patterns shift dramatically as cells transit from one phase of the cell cycle to another. To better define this transcriptional circuitry, we collected new microarray data across the cell cycle of budding yeast. The combined analysis of these data with three other cell cycle data sets identifies hundreds of new highly periodic transcripts and provides a weighted average peak time for each transcript. Using these data and phylogenetic comparisons of promoter sequences, we have identified a late S-phase-specific promoter element. This element is the binding site for the forkhead protein Hcm1, which is required for its cell cycle-specific activity. Among the cell cycle-regulated genes that contain conserved Hcm1-binding sites, there is a significant enrichment of genes involved in chromosome segregation, spindle dynamics, and budding. This may explain why Hcm1 mutants show 10-fold elevated rates of chromosome loss and require the spindle checkpoint for viability. Hcm1 also induces the M-phase-specific transcription factors FKH1, FKH2, and NDD1, and two cell cycle-specific transcriptional repressors, WHI5 and YHP1. As such, Hcm1 fills a significant gap in our understanding of the transcriptional circuitry that underlies the cell cycle.

Chromosome Segregation↗

PubMed1998

Protein kinase profile of sperm and eggs: cloning and characterization of two novel testis-specific protein kinases (AIE1, AIE2) related to yeast and fly chromosome segregation regulators.

We have analyzed the general protein kinase expression profile in mouse sperm and eggs. A total of 41 different kinases were identified. In this study, we describe two novel protein kinases, designated AIE1 (mouse) and AIE2 (human), which share high amino acid identities with the serine/threonine (S/T) kinase domain of yeast Ip11, fly aurora, and frog Eg2. Mutations in Ip11 and aurora have been reported to cause abnormal chromosome segregation and centrosome separation. Both AIE1 and AIE2 contain a typical S/T kinase domain (251 aa) flanked by a short polypeptide at both ends. Two other AIE-related kinases (STK-1 and IAK1/Ayk1) were also identified in mature mouse oocytes. The central kinase domain of AIE1 revealed 77.6% and 66.3% identity with that of STK-1 and IAK1/Ayk1, but much less homology was found in the sequence outside the kinase domain. Northern blot analysis revealed that both AIE1 and AIE2 are specifically expressed in testis, whereas STK-1 and IAK1/Ayk1 are expressed in many tissues rich in proliferating cells. An in vitro kinase assay showed that AIE1 can phosphorylate casein, AIE1 itself, and an uncharacterized cellular protein (p16). The kinase activity of AIE1 can be destroyed by heat inactivation. In summary, we suggest that AIE is a new member of the S/T kinase family, which may be regulated in a fashion distinct from other AIE-related kinases.

Amino Acid Sequence↗

PubMed2001

Bacterial chromosome segregation.

Recent years have witnessed a resurgence of interest in how the bacterial chromosome is organized and how newly replicated chromosomes are faithfully segregated into daughter cells on cell division. In the past, the problem with studying bacterial chromosomes was their lack of any obvious morphology, combined with the lack of ability to readily separate DNA replication and segregation functions into distinct stages like those observed in eukaryotic cells. This was due to the overlapping nature of these events in most bacterial systems used in the laboratory. The situation has now changed as new tools have become available that enable chromosomes and specific chromosomal sites to be labelled and monitored throughout the cell cycle, and this has led to rapid progress and the discovery of many unexpected results. Historically, chromosome segregation was thought to be achieved through passive processes where chromosomes were separated through some kind of membrane/cell wall attachment and were moved apart as the cell grew (Jacob et al., 1963). We now know that this is not the case and that there are specific mechanisms to actively partition chromosomes. This review will focus principally on the Gram-positive sporulating bacterium Bacillus subtilis, but will also cover work carried out on Escherichia coli, in which valuable information has been obtained, and will cover the events that occur on termination of chromosome replication, chromosome decatenation and chromosome separation.

Bacillus subtilis↗

PubMed2001

Fission yeast Bub1 is essential in setting up the meiotic pattern of chromosome segregation.

In meiosis, sister-chromatids move to the same spindle pole during the first division (MI) and to opposite poles during the second division (MII). This requires that MI sister kinetochores are co-orientated and form an apparent single functional unit that only interacts with microtubules from one pole, and that sister-chromatids remain associated through their centromeres until anaphase II. Here we investigate the function of Bub1 and Mad2, which are components of the mitotic-spindle checkpoint, on chromosome segregation during meiosis. Both proteins are required to prevent the occurrence of non-disjunction events in MI, which is consistent with recent findings that components of the mitotic-spindle checkpoint also operate during meiosis. However, Bub1 has several functions that are not shared with Mad2. When the bub1 gene is deleted, sister chromatids often move to opposite spindle poles during MI, indicating that sister kinetochores are disunited. Furthermore, the cohesin Rec8 is never retained at centromeres at anaphase I and sister-chromatid cohesion is lost. Our results show that Bub1, besides its functions in monitoring chromosome attachment, is essential for two other significant aspects of MI - unification of sister kinetochores and retention of centromeric cohesion.

Anaphase↗