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1.
Chromosome alignment on the mitotic spindle is monitored by the spindle checkpoint. We identify Sgo1, a protein involved in meiotic chromosome cohesion, as a spindle checkpoint component. Budding yeast cells with mutations in SGO1 respond normally to microtubule depolymerization but not to lack of tension at the kinetochore, and they have difficulty attaching sister chromatids to opposite poles of the spindle. Sgo1 is thus required for sensing tension between sister chromatids during mitosis, and its degradation when they separate may prevent cell cycle arrest and chromosome loss in anaphase, a time when sister chromatids are no longer under tension. 相似文献
2.
CARLSON JG 《Science (New York, N.Y.)》1956,124(3214):203-206
My conclusions, which, I confess, are tentative and based mainly on studies of one kind of cell, the grasshopper neuroblast, may be summarized as follows. The late prophase orientation of the chromosomes is a carry-over from the late telophase orientation. It is apparently maintained by means of the centromeres, which appear to be attached within a limited region of the nucleus throughout telophase, interphase, and prophase. Metaphase orientation of the chromosomes may be explained as the resultant of two forces: a force involving the centromere and spindle, which is responsible for keeping the centromeres in the equatorial plane of the spindle, and a repulsion force involving the noncentromeric portion of the chromosomes, which results in a tendency toward uniform spacing of the chromosomes outside the spindle. Anaphase separation of sister chromatids and their subsequent movement toward the poles of the spindle involves at least four distinct phases: (i) the initial poleward movement of the centromeres, which may be due to intrinsic repulsion or to a force acting between spindle and centromeres that produces an angle of almost 90 degrees between the separated and unseparated portions of the chromatids; (ii) the autonomous separation of the noncentromeric part of the chromosome; (iii) elongation of the spindle, beginning just after the sister chromatids are separated proximally and ending when the longer chromatids are about to lose contact distally; and (iv) the later movement apart of the daughter chromosomes, probably resulting from a pushing force exerted by elongation of the interzonal fibers. 相似文献
3.
The spindle checkpoint was characterized in meiosis of budding yeast. In the absence of the checkpoint, the frequency of meiosis I missegregation increased with increasing chromosome length, reaching 19% for the longest chromosome. Meiosis I nondisjunction in spindle checkpoint mutants could be prevented by delaying the onset of anaphase. In a recombination-defective mutant (spo11Delta), the checkpoint delays the biochemical events of anaphase I, suggesting that chromosomes that are attached to microtubules but are not under tension can activate the spindle checkpoint. Spindle checkpoint mutants reduce the accuracy of chromosome segregation in meiosis I much more than that in meiosis II, suggesting that checkpoint defects may contribute to Down syndrome. 相似文献
4.
Cohesins keep sister chromatids associated from the time of their replication in S phase until the onset of anaphase. In vertebrate cells, two distinct pathways dissociate cohesins, one acts on chromosome arms and the other on centromeres. Here, we describe a third pathway that acts on telomeres. Knockdown of tankyrase 1, a telomeric poly(ADP-ribose) polymerase caused mitotic arrest. Chromosomes aligned normally on the metaphase plate but were unable to segregate. Sister chromatids separated at centromeres and arms but remained associated at telomeres, apparently through proteinaceous bridges. Thus, telomeres may require a unique tankyrase 1-dependent mechanism for sister chromatid resolution before anaphase. 相似文献
5.
Centromeres are the structural elements of eukaryotic chromosomes that hold sister chromatids together and to which spindle tubules connect during cell division. Centromeres have been shown to suppress meiotic recombination in some systems. In this study yeast strains genetically marked within and flanking a centromere, were used to demonstrate that gene conversion (nonreciprocal recombination) tracts in mitosis can enter into and extend through the centromere. 相似文献
6.
After chromosome replication, sister chromatid copies are generally thought to segregate randomly to daughter cells. However, sister chromatids differ in their DNA strands, with each chromatid inheriting one older strand that is paired to a newly synthesized strand. Genetic analysis with a homologous chromosome pair indicated nonrandom chromatid distribution in embryonic stem cells. Biased segregation pattern was also found in all 100 endoderm cells examined, but not in any of the 165 neuroectoderm cells. In contrast, the mesoderm, cardiomyocyte, and pancreatic cells exhibited a random mode of segregation. Strand distribution mechanisms regulated by cell type may have consequences for cellular differentiation and for evolving strategies for developmental mechanisms. 相似文献
7.
Reproductive cells that are destined to become sperm or egg undergo meiotic division during which the chromosome number is halved. As Sluder and McCollum explain in their Perspective, new findings (Shonn et al.) in yeast show that there is a spindle checkpoint that operates during meiosis to ensure that an equal number of replicated chromosomes arrives at each pole of the cell. One of the components of this meiotic spindle checkpoint turns out to be Mad2, which gives the signal to halt meiosis if it looks like unequal chromosome segregation is taking place. 相似文献
8.
In eukaryotic cells, sister DNA molecules remain physically connected from their production at S phase until their separation during anaphase. This cohesion is essential for the separation of sister chromatids to opposite poles of the cell at mitosis. It also permits chromosome segregation to take place long after duplication has been completed. Recent work has identified a multisubunit complex called cohesin that is essential for connecting sisters. Proteolytic cleavage of one of cohesin's subunits may trigger sister separation at the onset of anaphase. 相似文献
9.
The spindle assembly checkpoint guards the fidelity of chromosome segregation. It requires the close cooperation of cell cycle regulatory proteins and cytoskeletal elements to sense spindle integrity. The role of the centrosome, the organizing center of the microtubule cytoskeleton, in the spindle checkpoint is unclear. We found that the molecular requirements for a functional spindle checkpoint included components of the large gamma-tubulin ring complex (gamma-TuRC). However, their localization at the centrosome and centrosome integrity were not essential for this function. Thus, the spindle checkpoint can be activated at the level of microtubule nucleation. 相似文献
10.
Nemergut ME Mizzen CA Stukenberg T Allis CD Macara IG 《Science (New York, N.Y.)》2001,292(5521):1540-1543
The Ran guanosine triphosphatase (GTPase) controls nucleocytoplasmic transport, mitotic spindle formation, and nuclear envelope assembly. These functions rely on the association of the Ran-specific exchange factor, RCC1 (regulator of chromosome condensation 1), with chromatin. We find that RCC1 binds directly to mononucleosomes and to histones H2A and H2B. RCC1 utilizes these histones to bind Xenopus sperm chromatin, and the binding of RCC1 to nucleosomes or histones stimulates the catalytic activity of RCC1. We propose that the docking of RCC1 to H2A/H2B establishes the polarity of the Ran-GTP gradient that drives nuclear envelope assembly, nuclear transport, and other nuclear events. 相似文献
11.
The spindle checkpoint delays sister chromatid separation until all chromosomes have undergone bipolar spindle attachment. Checkpoint failure may result in chromosome mis-segregation and may contribute to tumorigenesis. We showed that the human protein Hec1 was required for the recruitment of Mps1 kinase and Mad1/Mad2 complexes to kinetochores. Depletion of Hec1 impaired chromosome congression and caused persistent activation of the spindle checkpoint, indicating that high steady-state levels of Mad1/Mad2 complexes at kinetochores were not essential for checkpoint signaling. Simultaneous depletion of Hec1 and Mad2 caused catastrophic mitotic exit, making Hec1 an attractive target for the selective elimination of spindle checkpoint-deficient cells. 相似文献
12.
Proper chromosome segregation requires the attachment of sister kinetochores to microtubules from opposite spindle poles to form bi-oriented chromosomes on the metaphase spindle. The chromosome passenger complex containing Survivin and the kinase Aurora B regulates this process from the centromeres. We report that a de-ubiquitinating enzyme, hFAM, regulates chromosome alignment and segregation by controlling both the dynamic association of Survivin with centromeres and the proper targeting of Survivin and Aurora B to centromeres. Survivin is ubiquitinated in mitosis through both Lys(48) and Lys(63) ubiquitin linkages. Lys(63) de-ubiquitination mediated by hFAM is required for the dissociation of Survivin from centromeres, whereas Lys(63) ubiquitination mediated by the ubiquitin binding protein Ufd1 is required for the association of Survivin with centromeres. Thus, ubiquitinaton regulates dynamic protein-protein interactions and chromosome segregation independently of protein degradation. 相似文献
13.
Requirement of heterochromatin for cohesion at centromeres 总被引：1，自引：0，他引：1
Bernard P Maure JF Partridge JF Genier S Javerzat JP Allshire RC 《Science (New York, N.Y.)》2001,294(5551):2539-2542
Centromeres are heterochromatic in many organisms, but the mitotic function of this silent chromatin remains unknown. During cell division, newly replicated sister chromatids must cohere until anaphase when Scc1/Rad21-mediated cohesion is destroyed. In metazoans, chromosome arm cohesins dissociate during prophase, leaving centromeres as the only linkage before anaphase. It is not known what distinguishes centromere cohesion from arm cohesion. Fission yeast Swi6 (a Heterochromatin protein 1 counterpart) is a component of silent heterochromatin. Here we show that this heterochromatin is specifically required for cohesion between sister centromeres. Swi6 is required for association of Rad21-cohesin with centromeres but not along chromosome arms and, thus, acts to distinguish centromere from arm cohesion. Therefore, one function of centromeric heterochromatin is to attract cohesin, thereby ensuring sister centromere cohesion and proper chromosome segregation. 相似文献
14.
By the combination of cytological analysis and using genomic in situ hybridization technique to identify an alien chromosome in wheat-Haynaldia villosa monosomic addition lines, we studied the meiotic behavior of the alien chromosome. The results indicated that the frequency of bivalent pairing was lower than the value expected in PMCs of two monosomic addition lines, the frequency of wheat chromosomes unpairing increased, and the wheat homologous chromosome pairing was interfered with by the added chromosome 6V at metaphase I. The chromosome 6V lagged in 20.3% -29.3% of PMCs, sister chromatids 6V early divided in 29.0% - 34.1% of PMCs, the single chromosome 6V in 18.2% - 26.1% of PMCs went to a pole randomly,the breakage frequency of chromosome 6V was 1.2% - 2.9%. Meanwhile, it was also found that several wheat chromosomes showed earlier division, lagging and breakage in a few PMCs. It revealed that the added chromosome 6V influenced the behavior of wheat chromosomes at anaphase. It was also found that the translocation was produced between 6V and wheat chromosomes in 1.2% of PMCs. It offered evidence for translocation between wheat and Haynaldia villosa 6V chromosomes. 相似文献
15.
Tsai MY Wang S Heidinger JM Shumaker DK Adam SA Goldman RD Zheng Y 《Science (New York, N.Y.)》2006,311(5769):1887-1893
Mitotic spindle morphogenesis is a series of highly coordinated movements that lead to chromosome segregation and cytokinesis. We report that the intermediate filament protein lamin B, a component of the interphase nuclear lamina, functions in spindle assembly. Lamin B assembled into a matrix-like network in mitosis through a process that depended on the presence of the guanosine triphosphate-bound form of the small guanosine triphosphatase Ran. Depletion of lamin B resulted in defects in spindle assembly. Dominant negative mutant lamin B proteins that disrupt lamin B assembly in interphase nuclei also disrupted spindle assembly in mitosis. Furthermore, lamin B was essential for the formation of the mitotic matrix that tethers a number of spindle assembly factors. We propose that lamin B is a structural component of the long-sought-after spindle matrix that promotes microtubule assembly and organization in mitosis. 相似文献
16.
Cell division depends on the separation of sister chromatids in anaphase. In yeast, sister separation is initiated by cleavage of cohesin by the protease separase. In vertebrates, most cohesin is removed from chromosome arms by a cleavage-independent mechanism. Only residual amounts of cohesin are cleaved at the onset of anaphase, coinciding with its disappearance from centromeres. We have identified two separase cleavage sites in the human cohesin subunit SCC1 and have conditionally expressed noncleavable SCC1 mutants in human cells. Our results indicate that cohesin cleavage by separase is essential for sister chromatid separation and for the completion of cytokinesis. 相似文献
17.
The inner centromere-like protein (INCENP) forms a complex with the evolutionarily conserved family of Aurora Bkinases. The INCENP-Aurora complex helps coordinate chromosome segregation, spindle behavior, and cytokinesis during mitosis. INCENP-Aurora associates with kinetochores in metaphase and with spindle microtubules in anaphase, yet the trigger for this abrupt transfer is unknown. Here we show that the conserved phosphatase Cdc14 regulated the yeast INCENP-Aurora complex, Sli15-Ipl1. Cdc14 dephosphorylated Sli15 and thereby directed the complex to spindles. Activation of Cdc14 by separase was sufficient for Sli15 dephosphorylation and relocalization. Cdc14 not only regulates mitotic exit but also modulates spindle midzone assembly through Sli15-Ipl1. 相似文献
18.
Faithful chromosome segregation and repair of DNA double-strand breaks (DSBs) require cohesin, the protein complex that mediates sister-chromatid cohesion. Cohesion between sister chromatids is thought to be generated only during ongoing DNA replication by an obligate coupling between cohesion establishment factors such as Eco1 (Ctf7) and the replisome. Using budding yeast, we challenge this model by showing that cohesion is generated by an Eco1-dependent but replication-independent mechanism in response to DSBs in G(2)/M. Furthermore, our studies reveal that Eco1 has two functions: a cohesive activity and a conserved acetyltransferase activity, which triggers the generation of cohesion in response to the DSB and the DNA damage checkpoint. Finally, the DSB-induced cohesion is not limited to broken chromosomes but occurs also on unbroken chromosomes, suggesting that the DNA damage checkpoint through Eco1 provides genome-wide protection of chromosome integrity. 相似文献
19.
为了明确不同整形修剪模式下短枝富士苹果树体结构及各因素间的相关性,在河北省行唐县苹果标准示范园内,分别对自由纺锤型短枝富士、细长纺锤型短枝富士2个树形结构的树干尖削度以及其上着生小主枝轴的总粗度、平均粗度、总长度和平均长度进行了调查,并通过SPSS分析探讨了不同树形树干尖削度与其小主枝轴各生长指标的相关关系。结果表明:自由纺锤型短枝富士苹果的树干尖削度与其着生小主枝轴的总粗度、平均粗度、总长度和平均长度均呈负相关,但相关性均不显著;细长纺锤型短枝富士苹果的树干尖削度与其着生小主枝轴的总粗度呈负相关,与其他因素呈正相关,其中与小主枝轴平均长度的相关性达到了显著水平。本研究结果可为指导矮砧密植短枝富士苹果树整形技术提供科学依据。 相似文献
20.
Coordination of cytokinesis with chromosome congression and segregation is critical for proper cell division, but the mechanism is unknown. Here, septins, a conserved family of polymerizing guanosine triphosphate-binding proteins, localized to the metaphase plate during mitosis. Septin depletion resulted in chromosome loss from the metaphase plate, lack of chromosome segregation and spindle elongation, and incomplete cytokinesis upon delayed mitotic exit. These defects correlated with loss of the mitotic motor and the checkpoint regulator centromere-associated protein E (CENP-E) from the kinetochores of congressing chromosomes. Mammalian septins may thus form a mitotic scaffold for CENP-E and other effectors to coordinate cytokinesis with chromosome congression and segregation. 相似文献