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At least 613 records · Page 34Linked to original sources
PubMed2006

CDC2 phosphorylation of the fission yeast dis1 ensures accurate chromosome segregation.

Shortened kinetochore microtubules take separated chromatids to the opposing spindle poles in anaphase. Fission yeast Dis1 belongs to the Dis1/XMAP215/TOG family that is required for proper microtubule dynamics. Here, we report that Dis1is regulated by Cdc2 phosphorylation and that this mitotic phosphorylation ensures the fidelity of chromosome segregation. Whereas mutants Dis1(6A) and Dis1(6E) that substitute all of the six Cdc2 sites for Ala or Glu, respectively, produce colonies at 22 degrees C-36 degrees C, Dis1(6A) but not Dis1(6E) loses a minichromosome and reveals aberrant chromosome segregation at significant frequencies. Dis1(WT) is recruited to two regions of the mitotic spindle: kinetochores (possibly also kinetochore microtubules) in metaphase and the pole-to-pole microtubule lattice in anaphase. Mutant Dis1(6E) preferentially binds to metaphase kinetochores, whereas Dis1(6A), which is located along microtubules, fails in its accumulation at kinetochores. Dis1(6A) displays synthetic lethality with the mis12-537, which is a mutant that compromises kinetochore function. Dis1(6E) mimics the Cdc2-phosphorylated form of Dis1(WT), whereas Dis1(6A) can partially rescue the phenotype resulting form deletion of Mtc1/Alp14, another XMAP215-like protein. In anaphase, dephosphorylated Dis1 and Dis1(6A), but not Dis1(6E), move to the spindle microtubule lattice near the SPBs. Cdc2 thus directly phosphorylates Dis1, and this phosphorylation regulates Dis1 localization in both metaphase and anaphase and ensures high-fidelity segregation.

CDC2 Protein Kinase↗
PubMed2004

Structure and segregation of the bacterial nucleoid.

In bacteria, chromosome segregation and DNA replication occur concurrently and there is no clear equivalent of a eukaryote mitotic spindle. Chromosome segregation can be viewed as a two-step process. As the first step, the origin of replication regions are segregated actively, probably by a mechanism involving an as yet unidentified motor protein or proteins, and held in position. The second step is the separation and migration of the rest of the chromosome probably driven by forces generated from various cellular processes such as DNA replication, transcription and transertion.

Bacillus subtilis↗
PubMed2004

DNA replication checkpoint prevents precocious chromosome segregation by regulating spindle behavior.

The DNA replication checkpoint maintains replication fork integrity and prevents chromosome segregation during replication stresses. Mec1 and Rad53 (human ATM/ATR- and Chk2-like kinases, respectively) are critical effectors of this pathway in yeast. When treated with replication inhibitors, checkpoint-deficient mec1 or rad53 mutant fails to maintain replication fork integrity and proceeds to partition unreplicated chromosomes. We show that this unnatural chromosome segregation requires neither the onset of mitosis nor APC activation, cohesin cleavage, or biorientation of kinetochores. Instead, the checkpoint deficiency leads to deregulation of microtubule-associated proteins Cin8 and Stu2, which, in the absence of both chromosome cohesion and bipolar attachment of kinetochores to microtubules, induce untimely spindle elongation, causing premature chromosome separation. The checkpoint's ability to prevent nuclear division is abolished by combined deficiency of microtubule-destabilizing motor Kip3 and Mad2 functions. Thus, the DNA replication checkpoint prevents precocious chromosome segregation, not by inhibiting entry into mitosis as widely believed, but by directly regulating spindle dynamics.

Blotting, Northern↗
PubMed2005

Bacterial DNA segregation by the actin-like MreB protein.

Faithful chromosome segregation is vital to all organisms. Eukaryotic cells use the tubulin-based cytoskeleton to segregate their chromosomes during mitosis. A handful of papers have provided convincing evidence that, in bacteria, this task is accomplished by the actin homolog MreB. In particular, a recent study by Gitai et al. demonstrates that MreB specifically binds to and segregates the replication origin of the bacterial chromosome.

Actins↗
PubMed2003

Clustering versus random segregation of plasmids lacking a partitioning function: a plasmid paradox?

Plasmids lacking a functional partition system are randomly distributed to the daughter cells; plasmid-free daughter cells are formed with a frequency of (1/2)2n per cell and cell generation where 2n is the (average) copy number at cell division. Hence, the unit of segregation is one plasmid copy. However, plasmids form clusters in the cells. A putative solution to this potential paradox is presented: one plasmid copy at a time is recruited from the plasmid clusters to the replication factories that are located in the cell centres. Hence, replication offers the means of declustering that is necessary in a growing host population. The daughter copies diffuse freely and each copy may with equal probability end up in either of the two cell halves. In this way, the random segregation of the plasmids is coupled to replication and occurs continuously during the cell cycle, and is not linked to cell division. The unit of segregation is the plasmid copy and not the plasmid clusters. In contrast, the two daughters of a Par+ plasmid are directed in opposite directions by the plasmid-encoded partition system, thereby assuring that each daughter cell receives the plasmid.

Bacterial Proteins↗
PubMed1999

Chromosome segregation during the prokaryotic cell division cycle.

Recent work has dramatically changed our view of chromosome segregation in bacteria. Rather than being a passive process, it involves rapid movement of parts of the circular chromosome. Several genes involved in chromosome segregation have been identified, and the analysis of their functions and intracellular localization are beginning to shed light on the mechanisms that ensure efficient chromosome segregation.

Bacillus subtilis↗
PubMed2003

The nature of DNA plays a role in chromosome segregation: endoreduplication in halogen-substituted chromosomes.

AA8 Chinese hamster ovary cells were treated with halogenated nucleosides analogues of thymidine, namely CldU, 5-iodo-2'-deoxyuridine (IdU), and 5-bromo-2'-deoxyuridine (BrdU), following different experimental protocols. The purpose was to see whether incorporation of exogenous pyrimidine analogues into DNA could interfere with normal chromosome segregation. The endpoint chosen was endoreduplication, that arises after aberrant mitosis when daughter chromatids segregation fails. Treatment with any of the halogenated nucleosides for two consecutive cell cycles resulted in endoreduplication, with a highest yield for CldU, intermediate for IdU, and lowest for BrdU. The frequency of endoreduplicated cells paralleled in all cases the level of analogue substitution into DNA. Our results seem to support that thymidine analogue substitution into DNA is responsible for the triggering of endoreduplication. Besides, the lack of any effect on endoreduplication when CldU was present for only one S-period strongly suggest that it is the nature of template, and not nascent DNA, that plays a major role in chromosome segregation. Taking into account that topoisomerase II cleaves DNA at preferred sequences within its recognition/binding sites, the likely involvement of the enzyme is discussed.

Animals↗
PubMed2004

"Holo"er than thou: chromosome segregation and kinetochore function in C. elegans.

Kinetochores are proteinaceous organelles that assemble on centromeric DNA to direct chromosome segregation in all eukaryotes. While many aspects of kinetochore function are conserved, the nature of the chromosomal domain upon which kinetochores assemble varies dramatically between different species. In monocentric eukaryotes, kinetochores assemble on a localized region of each chromosome. In contrast, holocentric species such as the nematode Caenorhabditis elegans have diffuse kinetochores that form along the entire length of their chromosomes. Here, we discuss the nature of chromosome segregation in C. elegans. In addition to reviewing what is known about kinetochore function, chromosome structure, and chromosome movement, we consider the consequences of the specialized holocentric architecture on chromosome segregation.

Animals↗
PubMed2001

Pre-meiotic S phase is linked to reductional chromosome segregation and recombination.

Meiosis is initiated from G1 of the cell cycle and is characterized by a pre-meiotic S phase followed by two successive nuclear divisions. The first of these, meiosis I, differs from mitosis in having a reductional pattern of chromosome segregation. Here we show that meiosis can be initiated from G2 in fission yeast cells by ectopically activating the meiosis-inducing network. The subsequent meiosis I occurs without a pre-meiotic S phase and with decreased recombination, and exhibits a mitotic pattern of equational chromosome segregation. The subsequent meiosis II results in random chromosome segregation. This behaviour is similar to that observed in cells lacking the meiotic cohesin Rec8 (refs 3, 4), which becomes associated with chromosomes at G1/S phase, including the inner centromere, a region that is probably critical for sister-centromere orientation. If the expression of Rec8 is delayed to S phase/G2, then the centromeres behave equationally. We propose that the presence of Rec8 in chromatin is required at the pre-meiotic S phase to construct centromeres that behave reductionally and chromosome arms capable of a high level of recombination, and that this explains why meiosis is initiated from G1 of the cell cycle.

Chromosome Segregation↗
PubMed2005

SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions.

Structure chromosome (SMC) proteins organize the core of cohesin, condensin and Smc5-Smc6 complexes. The Smc5-Smc6 complex is required for DNA repair, as well as having another essential but enigmatic function. Here, we generated conditional mutants of SMC5 and SMC6 in budding yeast, in which the essential function was affected. We show that mutant smc5-6 and smc6-9 cells undergo an aberrant mitosis in which chromosome segregation of repetitive regions is impaired; this leads to DNA damage and RAD9-dependent activation of the Rad53 protein kinase. Consistent with a requirement for the segregation of repetitive regions, Smc5 and Smc6 proteins are enriched at ribosomal DNA (rDNA) and at some telomeres. We show that, following Smc5-Smc6 inactivation, metaphase-arrested cells show increased levels of X-shaped DNA (Holliday junctions) at the rDNA locus. Furthermore, deletion of RAD52 partially suppresses the temperature sensitivity of smc5-6 and smc6-9 mutants. We also present evidence showing that the rDNA segregation defects of smc5/smc6 mutants are mechanistically different from those previously observed for condensin mutants. These results point towards a role for the Smc5-Smc6 complex in preventing the formation of sister chromatid junctions, thereby ensuring the correct partitioning of chromosomes during anaphase.

Cell Cycle Proteins↗
PubMed2005

Bacterial DNA segregation dynamics mediated by the polymerizing protein ParF.

Prokaryotic DNA segregation most commonly involves members of the Walker-type ParA superfamily. Here we show that the ParF partition protein specified by the TP228 plasmid is a ParA ATPase that assembles into extensive filaments in vitro. Polymerization is potentiated by ATP binding and does not require nucleotide hydrolysis. Analysis of mutations in conserved residues of the Walker A motif established a functional coupling between filament dynamics and DNA partitioning. The partner partition protein ParG plays two separable roles in the ParF polymerization process. ParF is unrelated to prokaryotic polymerizing proteins of the actin or tubulin families, but is a homologue of the MinD cell division protein, which also assembles into filaments. The ultrastructures of the ParF and MinD polymers are remarkably similar. This points to an evolutionary parallel between DNA segregation and cytokinesis in prokaryotic cells, and reveals a potential molecular mechanism for plasmid and chromosome segregation mediated by the ubiquitous ParA-type proteins.

1-Acylglycerol-3-Phosphate O-Acyltransferase↗
PubMed2006

Testing for segregation distortion in genetic scoring data from backcross or doubled haploid populations.

It is important that breeders have the means to assess genetic scoring data for segregation distortion because of its probable effect on the design of efficient breeding strategies. Scoring data is usually assessed for segregation distortion by separate nonindependent chi2 tests at each locus in a set of marker loci. This analysis gives the loci most affected by selection if it exists, but it cannot give a statistically correct test for the presence or absence of selection in a linkage group as a whole. I have used a combined test based on the statistic, which is the most significant P-value from the above tests, called the single locus test. I have also derived mathematically a new combined statistical test, the overall test, for segregation distortion that requires genetic scoring data for a single linkage group. This test also takes genetic linkage into account. Using a range of marker densities and population sizes, simulations were carried out, to compare the power of these two statistical tests to detect the effect of selection at one or two loci. The single locus test was always found to be more powerful than the overall test, but the single locus test required a more complicated P-value correction. For the single locus test, approximate correction factors for the P-values are given for a range of marker densities and genetic lengths.

Chi-Square Distribution↗
PubMed2003

A strand-specific model for chromosome segregation in bacteria.

Chromosome separation and segregation must be executed within a bacterial cell in which the membrane and cytoplasm are highly structured. Here, we develop a strand-specific model based on each of the future daughter chromosomes being associated with a different set of structures or hyperstructures in an asymmetric cell. The essence of the segregation mechanism is that the genes on the same strand in the parental cell that are expressed together in a hyperstructure continue to be expressed together and segregate together in the daughter cell. The model therefore requires an asymmetric distribution of classes of genes and of binding sites and other structures on the strands of the parental chromosome. We show that the model is consistent with the asymmetric distribution of highly expressed genes and of stress response genes in Escherichia coli and Bacillus subtilis. The model offers a framework for interpreting data from genomics.

Bacillus subtilis↗
PubMed1998

Human aneuploidy: lessons from achiasmate segregation in Drosophila melanogaster.

Aneuploidy is a crucial issue in human reproductive biology, accounting for both a significant proportion of miscarriages and, among liveborns, multiple congenital malformation syndromes such as Down Syndrome. Although the etiology of human aneuploidy remains poorly understood, recent studies have elucidated certain fundamental correlates of meiotic nondisjunction, such as altered recombination. These features are extraordinarily similar to those associated with chromosome misbehavior in Drosophila melanogaster females. Furthermore, these organisms also share a significant level of achiasmate chromosome nondisjunction. Here we describe in detail the processes of achiasmate chromosome segregation in Drosophila and discuss how they may be most effectively applied to our understanding of the etiology of human aneuploidy. In particular, we examine the possibility that similar "backup" mechanisms of chromosome segregation might function in mammalian meiosis, particularly mammalian females. Drawing upon observations made in flies, we also propose a new model for the segregation of achiasmate chromosomes in humans.

Aneuploidy↗
PubMed2002

Segregation distortion induced by wild-type RanGAP in Drosophila.

Segregation Distorter (SD) is a meiotic drive system in Drosophila that causes preferential transmission of the SD chromosome from SD/SD(+) males owing to the induced dysfunction of SD(+) spermatids. The key distorter locus, Sd, is a dominant neomorphic allele encoding a truncated, but enzymatically active, RanGAP (RanGTPase-activating protein) whose nuclear mislocalization underlies distortion by disrupting the Ran signaling pathway. Here, we show that even wild-type RanGAP can cause segregation distortion when it is overexpressed in the male germ line or when the gene dosage of a particular modifier locus is increased. Both manipulations result in substantial nuclear accumulation of RanGAP. Distortion can be suppressed by overexpression of Ran or Ran guanine nucleotide exchange factor (RanGEF) in the male germ line, indicating that the primary consequence of nuclear mislocalization of RanGAP is reduction of intranuclear RanGTP levels. These results prove that segregation distortion does not depend on any unique properties of the mutant RanGAP encoded by Sd and provide a unifying explanation for the occurrence of distortion in a variety of experimental situations.

Animals↗
PubMed2001

Meiotic recombination and chromosome segregation in Schizosaccharomyces pombe.

In most organisms homologous recombination is vital for the proper segregation of chromosomes during meiosis, the formation of haploid sex cells from diploid precursors. This review compares meiotic recombination and chromosome segregation in the fission yeast Schizosaccharomyces pombe and the distantly related budding yeast Saccharomyces cerevisiae, two especially tractable microorganisms. Certain features, such as the occurrence of DNA breaks associated with recombination, appear similar, suggesting that these features may be common in eukaryotes. Other features, such as the role of these breaks and the ability of chromosomes to segregate faithfully in the absence of recombination, appear different, suggesting multiple solutions to the problems faced in meiosis.

Animals↗
PubMed1999

Mutations in the alpha-tubulin 67C gene specifically impair achiasmate segregation in Drosophila melanogaster.

Drosophila melanogaster oocytes heterozygous for mutations in the alpha-tubulin 67C gene (alphatub67C) display defects in centromere positioning during prometaphase of meiosis I. The centromeres do not migrate to the poleward edges of the chromatin mass, and the chromatin fails to stretch during spindle lengthening. These results suggest that the poleward forces acting at the kinetochore are compromised in the alphatub67C mutants. Genetic studies demonstrate that these mutations also strongly and specifically decrease the fidelity of achiasmate chromosome segregation. Proper centromere orientation, chromatin elongation, and faithful segregation can all be restored by a decrease in the amount of the Nod chromokinesin. These results suggest that the accurate segregation of achiasmate chromosomes requires the proper balancing of forces acting on the chromosomes during prometaphase.

Animals↗
PubMed2000

Partitioning of the 2-microm circle plasmid of Saccharomyces cerevisiae. Functional coordination with chromosome segregation and plasmid-encoded rep protein distribution.

The efficient partitioning of the 2-microm plasmid of Saccharomyces cerevisiae at cell division is dependent on two plasmid-encoded proteins (Rep1p and Rep2p), together with the cis-acting locus REP3 (STB). In addition, host encoded factors are likely to contribute to plasmid segregation. Direct observation of a 2-microm-derived plasmid in live yeast cells indicates that the multiple plasmid copies are located in the nucleus, predominantly in clusters with characteristic shapes. Comparison to a single-tagged chromosome or to a yeast centromeric plasmid shows that the segregation kinetics of the 2-microm plasmid and the chromosome are quite similar during the yeast cell cycle. Immunofluorescence analysis reveals that the plasmid is colocalized with the Rep1 and Rep2 proteins within the yeast nucleus. Furthermore, the Rep proteins (and therefore the plasmid) tend to concentrate near the poles of the yeast mitotic spindle. Depolymerization of the spindle results in partial dispersion of the Rep proteins in the nucleus concomitant with a loosening in the association between plasmid molecules. In an ipl1-2 yeast strain, shifted to the nonpermissive temperature, the chromosomes and plasmid almost always missegregate in tandem. Our results suggest that, after DNA replication, plasmid distribution to the daughter cells occurs in the form of specific DNA-protein aggregates. They further indicate that the plasmid partitioning mechanism may exploit at least some of the components of the cellular machinery required for chromosomal segregation.

Cell Cycle↗