scholarly journals Geometric partitioning of cohesin and condensin is a consequence of chromatin loops

2018 ◽  
Vol 29 (22) ◽  
pp. 2737-2750 ◽  
Author(s):  
Josh Lawrimore ◽  
Ayush Doshi ◽  
Brandon Friedman ◽  
Elaine Yeh ◽  
Kerry Bloom
Keyword(s):  
Mitotic Spindle ◽  
Chromosome Organization ◽  
Ideal Model ◽  
Pericentric Region ◽  
Chromatin Loops ◽  
Axial Tension ◽  
Sister Chromatids ◽  
Geometric Partitioning ◽  
Structural Maintenance Of Chromosomes

SMC (structural maintenance of chromosomes) complexes condensin and cohesin are crucial for proper chromosome organization. Condensin has been reported to be a mechanochemical motor capable of forming chromatin loops, while cohesin passively diffuses along chromatin to tether sister chromatids. In budding yeast, the pericentric region is enriched in both condensin and cohesin. As in higher-eukaryotic chromosomes, condensin is localized to the axial chromatin of the pericentric region, while cohesin is enriched in the radial chromatin. Thus, the pericentric region serves as an ideal model for deducing the role of SMC complexes in chromosome organization. We find condensin-mediated chromatin loops establish a robust chromatin organization, while cohesin limits the area that chromatin loops can explore. Upon biorientation, extensional force from the mitotic spindle aggregates condensin-bound chromatin from its equilibrium position to the axial core of pericentric chromatin, resulting in amplified axial tension. The axial localization of condensin depends on condensin’s ability to bind to chromatin to form loops, while the radial localization of cohesin depends on cohesin’s ability to diffuse along chromatin. The different chromatin-tethering modalities of condensin and cohesin result in their geometric partitioning in the presence of an extensional force on chromatin.

scholarly journals Merotelic kinetochores in mammalian tissue cells

2005 ◽  
Vol 360 (1455) ◽  
pp. 553-568 ◽  
Author(s):  
E.D Salmon ◽  
D Cimini ◽  
L.A Cameron ◽  
J.G DeLuca
Keyword(s):  
Mitotic Spindle ◽  
Binding Sites ◽  
Metaphase Plate ◽  
Mammalian Tissue ◽  
Anaphase Onset ◽  
Sister Chromatids ◽  
Pulling Forces ◽  
Tissue Cells ◽  
Early Mitosis

Merotelic kinetochore attachment is a major source of aneuploidy in mammalian tissue cells in culture. Mammalian kinetochores typically have binding sites for about 20–25 kinetochore microtubules. In prometaphase, kinetochores become merotelic if they attach to microtubules from opposite poles rather than to just one pole as normally occurs. Merotelic attachments support chromosome bi-orientation and alignment near the metaphase plate and they are not detected by the mitotic spindle checkpoint. At anaphase onset, sister chromatids separate, but a chromatid with a merotelic kinetochore may not be segregated correctly, and may lag near the spindle equator because of pulling forces toward opposite poles, or move in the direction of the wrong pole. Correction mechanisms are important for preventing segregation errors. There are probably more than 100 times as many PtK1 tissue cells with merotelic kinetochores in early mitosis, and about 16 times as many entering anaphase as the 1% of cells with lagging chromosomes seen in late anaphase. The role of spindle mechanics and potential functions of the Ndc80/Nuf2 protein complex at the kinetochore/microtubule interface is discussed for two correction mechanisms: one that functions before anaphase to reduce the number of kinetochore microtubules to the wrong pole, and one that functions after anaphase onset to move merotelic kinetochores based on the ratio of kinetochore microtubules to the correct versus incorrect pole.

scholarly journals Intermediates in the assembly of mitotic checkpoint complexes and their role in the regulation of the anaphase-promoting complex

2016 ◽  
Vol 113 (4) ◽  
pp. 966-971 ◽  
Author(s):  
Sharon Kaisari ◽  
Danielle Sitry-Shevah ◽  
Shirly Miniowitz-Shemtov ◽  
Avram Hershko
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Spindle Assembly Checkpoint ◽  
Mitotic Checkpoint ◽  
Anaphase Promoting Complex ◽  
Checkpoint Proteins ◽  
Sister Chromatids ◽  
Unknown Species ◽  
Mitotic Checkpoint Complex

The mitotic (or spindle assembly) checkpoint system prevents premature separation of sister chromatids in mitosis and thus ensures the fidelity of chromosome segregation. Kinetochores that are not attached properly to the mitotic spindle produce an inhibitory signal that prevents progression into anaphase. The checkpoint system acts on the Anaphase-Promoting Complex/Cyclosome (APC/C) ubiquitin ligase, which targets for degradation inhibitors of anaphase initiation. APC/C is inhibited by the Mitotic Checkpoint Complex (MCC), which assembles when the checkpoint is activated. MCC is composed of the checkpoint proteins BubR1, Bub3, and Mad2, associated with the APC/C coactivator Cdc20. The intermediary processes in the assembly of MCC are not sufficiently understood. It is also not clear whether or not some subcomplexes of MCC inhibit the APC/C and whether Mad2 is required only for MCC assembly and not for its action on the APC/C. We used purified subcomplexes of mitotic checkpoint proteins to examine these problems. Our results do not support a model in which Mad2 catalytically generates a Mad2-free APC/C inhibitor. We also found that the release of Mad2 from MCC caused a marked (although not complete) decrease in inhibitory action, suggesting a role of Mad2 in MCC for APC/C inhibition. A previously unknown species of MCC, which consists of Mad2, BubR1, and two molecules of Cdc20, contributes to the inhibition of APC/C by the mitotic checkpoint system.

scholarly journals Contribution of hCAP-D2, a Non-SMC Subunit of Condensin I, to Chromosome and Chromosomal Protein Dynamics during Mitosis

2005 ◽  
Vol 25 (2) ◽  
pp. 740-750 ◽  
Author(s):  
Erwan Watrin ◽  
Vincent Legagneux
Keyword(s):  
Rna Interference ◽  
Mitotic Spindle ◽  
Topoisomerase Ii ◽  
Mitotic Chromosome ◽  
Chromosomal Protein ◽  
Structural Components ◽  
Mitotic Chromosomes ◽  
Sister Chromatids ◽  
Chromosome Alignment ◽  
Structural Maintenance Of Chromosomes

ABSTRACT Condensins are heteropentameric complexes that were first identified as structural components of mitotic chromosomes. They are composed of two SMC (structural maintenance of chromosomes) and three non-SMC subunits. Condensins play a role in the resolution and segregation of sister chromatids during mitosis, as well as in some aspects of mitotic chromosome assembly. Two distinct condensin complexes, condensin I and condensin II, which differ only in their non-SMC subunits, exist. Here, we used an RNA interference approach to deplete hCAP-D2, a non-SMC subunit of condensin I, in HeLa cells. We found that the association of hCAP-H, another non-SMC subunit of condensin I, with mitotic chromosomes depends on the presence of hCAP-D2. Moreover, chromatid axes, as defined by topoisomerase II and hCAP-E localization, are disorganized in the absence of hCAP-D2, and the resolution and segregation of sister chromatids are impaired. In addition, hCAP-D2 depletion affects chromosome alignment in metaphase and delays entry into anaphase. This suggests that condensin I is involved in the correct attachment between chromosome kinetochores and microtubules of the mitotic spindle. These results are discussed relative to the effects of depleting both condensin complexes.

The Role of the Centrosome in Development and Progression of Breast Cancer

2001 ◽  
Vol 7 (S2) ◽  
pp. 582-583
Author(s):  
W. Lingle ◽  
J. Salisbury ◽  
S. Barrett ◽  
V. Negron ◽  
C. Whitehead
Keyword(s):  
Mitotic Spindle ◽  
Mammalian Cells ◽  
Microtubule Organizing Center ◽  
Daughter Cells ◽  
Spindle Poles ◽  
Sister Chromatids ◽  
Close Proximity ◽  
Interphase Cells ◽  
Organizing Center

The centrosome is the major microtubule organizing center in most mammalian cells, and as such it determines the number, polarity, and spatial distribution of microtubules (MTs). Interphase MTs, together with actin and intermediate filaments, constitute the cell's cytoskeleton, which dynamically maintains cell polarity and tissue architecture. Interphase cells begin Gl of the cell cycle with one centrosome. During S phase, the centrosome duplicates concomitantly with DNA replication. Duplicated centrosomes usually remain in close proximity to one another until late G2, at which time they separate and then move during prophase to become the poles that organize the bipolar mitotic spindle. During the G2/M transition, interphase MTs depolymerize and a new population of highly dynamic mitotic MTs are nucleated at the spindle poles. The bipolar mitotic spindle apparatus constitutes the machinery that partitions and separates sister chromatids equally between two daughter cells.

scholarly journals Cohesin-independent segregation of sister chromatids in budding yeast

2012 ◽  
Vol 23 (4) ◽  
pp. 729-739 ◽  
Author(s):  
Vincent Guacci ◽  
Douglas Koshland
Keyword(s):  
Mitotic Spindle ◽  
Budding Yeast ◽  
Alternative Mechanism ◽  
Yeast Viability ◽  
Sister Chromatids ◽  
Damage Repair ◽  
Independent Segregation ◽  
Independent Mechanism ◽  
Cohesin Subunit

Cohesin generates cohesion between sister chromatids, which enables chromosomes to form bipolar attachments to the mitotic spindle and segregate. Cohesin also functions in chromosome condensation, transcriptional regulation, and DNA damage repair. Here we analyze the role of acetylation in modulating cohesin functions and how it affects budding yeast viability. Previous studies show that cohesion establishment requires Eco1p-mediated acetylation of the cohesin subunit Smc3p at residue K113. Smc3p acetylation was proposed to promote establishment by merely relieving Wpl1p inhibition because deletion of WPL1 bypasses the lethality of an ECO1 deletion (eco1Δ wpl1Δ). We find that little, if any, cohesion is established in eco1Δ wpl1Δ cells, indicating that Eco1p performs a function beyond antagonizing Wpl1p. Cohesion also fails to be established when SMC3 acetyl-mimics (K113Q or K112R,K113Q) are the sole functional SMC3s in cells. These results suggest that Smc3p acetylation levels affect establishment. It is remarkable that, despite their severe cohesion defect, eco1Δ wpl1Δ and smc3-K112R,K113Q strains are viable because a cohesin-independent mechanism enables bipolar attachment and segregation. This alternative mechanism is insufficient for smc3-K113Q strain viability. Smc3-K113Q is defective for condensation, whereas eco1Δ wpl1Δ and smc3-K112R,K113Q strains are competent for condensation. We suggest that Smc3p acetylation and Wpl1p antagonistically regulate cohesin's essential role in condensation.

Distribution and function of non-histone proteins in human chromosomes

1992 ◽  
Vol 50 (1) ◽  
pp. 556-557
Author(s):  
W.C. Earnshaw ◽  
C.A. Cooke
Keyword(s):  
Mitotic Spindle ◽  
Centromeric Heterochromatin ◽  
Mitotic Chromosomes ◽  
Histone Proteins ◽  
Sister Chromatids ◽  
Structural Specialization ◽  
And Function ◽  
Passenger Proteins

The role of non-histone proteins in the structure and movements of mitotic chromosomes remains poorly understood. We describe here experiments aimed at characterization of the distribution of two very different classes of these proteins. The first is composed of integral components of the centromere (or primary constriction). The second class consists of proteins that we have termed “chromosome passenger proteins”. These proteins are chromosomal during most of the cell cycle, but appear to be associated with the cytoskeleton during anaphase and telophase.The centromere regions of chromosomes perform three essential functions in mitosis. (1) They form the site of attachment of the chromosomes to the mitotic spindle. (2) They contain the mechanochemical motor molecules that are responsible for the movements of the chromosomes along microtubules. (3) They regulate the pairing of sister chromatids during mitosis. The first two of these mitotic functions are properties of a disk-shaped structural specialization, the kinetochore, which is located at the surface of the centromeric heterochromatin.

Cohesin dependent compaction of mitotic chromosomes

2016 ◽  
Author(s):  
Stephanie A Schalbetter ◽  
Anton Goloborodko ◽  
Geoffrey Fudenberg ◽  
Jon M Belton ◽  
Catrina Miles ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Mitotic Chromosome ◽  
Protein Complexes ◽  
Budding Yeast ◽  
Mitotic Chromosomes ◽  
Chromosome Conformation ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Structural Maintenance Of Chromosomes

Structural Maintenance of Chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply-conserved SMC complexes, organize chromosomes in budding yeast. The canonical role of cohesins is to co-align sister chromatids whilst condensins generally compact mitotic chromosomes. We find strikingly different roles in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosomes arms, independent of and in addition to its role in sister-chromatid cohesion. Cohesin dependent mitotic chromosome compaction can be fully accounted for through cis-looping of chromatin by loop extrusion. Second, condensin is dispensable for compaction along chromosomal arms and instead plays a specialized role, structuring rDNA and peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that SMC-dependent looping is readily deployed in a range of contexts to functionally organize chromosomes.

PTTG has a Dual Role of Promotion-Inhibition in the Development of Pituitary Adenomas

2019 ◽  
Vol 26 (11) ◽  
pp. 800-818
Author(s):  
Zujian Xiong ◽  
Xuejun Li ◽  
Qi Yang
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Cell Cycle Progression ◽  
Key Factors ◽  
Cycle Progression ◽  
Sister Chromatids ◽  
Regulation Of Cell Cycle ◽  
Late Stages

Pituitary Tumor Transforming Gene (PTTG) of human is known as a checkpoint gene in the middle and late stages of mitosis, and is also a proto-oncogene that promotes cell cycle progression. In the nucleus, PTTG works as securin in controlling the mid-term segregation of sister chromatids. Overexpression of PTTG, entering the nucleus with the help of PBF in pituitary adenomas, participates in the regulation of cell cycle, interferes with DNA repair, induces genetic instability, transactivates FGF-2 and VEGF and promotes angiogenesis and tumor invasion. Simultaneously, overexpression of PTTG induces tumor cell senescence through the DNA damage pathway, making pituitary adenoma possessing the potential self-limiting ability. To elucidate the mechanism of PTTG in the regulation of pituitary adenomas, we focus on both the positive and negative function of PTTG and find out key factors interacted with PTTG in pituitary adenomas. Furthermore, we discuss other possible mechanisms correlate with PTTG in pituitary adenoma initiation and development and the potential value of PTTG in clinical treatment.

scholarly journals Genes Involved in Sister Chromatid Separation and Segregation in the Budding Yeast Saccharomyces cerevisiae

Genetics ◽  
2001 ◽  
Vol 159 (2) ◽  
pp. 453-470
Author(s):  
Sue Biggins ◽  
Needhi Bhalla ◽  
Amy Chang ◽  
Dana L Smith ◽  
Andrew W Murray
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Mitotic Spindle ◽  
Budding Yeast ◽  
Temperature Sensitive ◽  
Chromosome Behavior ◽  
Yeast Saccharomyces Cerevisiae ◽  
Sister Chromatids ◽  
Marked Chromosome ◽  
Sister Chromatid Separation

Abstract Accurate chromosome segregation requires the precise coordination of events during the cell cycle. Replicated sister chromatids are held together while they are properly attached to and aligned by the mitotic spindle at metaphase. At anaphase, the links between sisters must be promptly dissolved to allow the mitotic spindle to rapidly separate them to opposite poles. To isolate genes involved in chromosome behavior during mitosis, we microscopically screened a temperature-sensitive collection of budding yeast mutants that contain a GFP-marked chromosome. Nine LOC (loss of cohesion) complementation groups that do not segregate sister chromatids at anaphase were identified. We cloned the corresponding genes and performed secondary tests to determine their function in chromosome behavior. We determined that three LOC genes, PDS1, ESP1, and YCS4, are required for sister chromatid separation and three other LOC genes, CSE4, IPL1, and SMT3, are required for chromosome segregation. We isolated alleles of two genes involved in splicing, PRP16 and PRP19, which impair α-tubulin synthesis thus preventing spindle assembly, as well as an allele of CDC7 that is defective in DNA replication. We also report an initial characterization of phenotypes associated with the SMT3/SUMO gene and the isolation of WSS1, a high-copy smt3 suppressor.

scholarly journals 4-hydroxyphenylpyruvate dioxygenase thermolability is responsible for temperature-dependent melanogenesis inAeromonas salmonicidasubsp.salmonicida

2018 ◽  
Author(s):  
Yunqian Qiao ◽  
Jiao Wang ◽  
He Wang ◽  
Baozhong Chai ◽  
Chufeng Rao ◽  
...  
Keyword(s):  
Cold Water ◽  
Biological Significance ◽  
Adaptive Strategy ◽  
Aeromonas Salmonicida ◽  
Temperature Dependent ◽  
Ideal Model ◽  
Melanin Production ◽  
Water Fish ◽  
Insight Into

AbstractAeromonas salmonicidasubsp.salmonicida(A.s.s) is a major pathogen affecting fisheries worldwide. It is a well-known member of the pigmentedAeromonasspecies, which produces melanin at ≤ 22 °C. However, melanogenesis decreases as the culture temperature increases and is completely suppressed at 30-35 °C while bacterial growth is not affected. The mechanism and biological significance of this temperature-dependent melanogenesis are not clear. Heterologous expression of anA.s.s.4-hydroxyphenylpyruvate dioxygenase (HppD), the most crucial enzyme in the HGA-melanin synthesis pathway, results in thermosensitive pigmentation inEscherichia coli, suggesting that HppD plays a key role in this process. In the current study, we demonstrated that the extreme thermolability of HppD is responsible for the temperature-dependent melanization ofA.s.s.Substitutions in three residues, Ser18, Pro103, or Leu119 of HppD fromA.s.sincreases the thermolability of this enzyme and results in temperature-independent melanogenesis. Moreover, replacing the corresponding residues of HppD fromAeromonasmedia strain WS, which forms pigment independent of temperature, with those ofA.s.sHppD leads to thermosensitive melanogenesis. Structural analysis suggested that mutations at these sites, especially at position P103, can strengthen the secondary structure of HppD and greatly improve its thermal stability. In addition, we found that HppD sequences of allA.s.sisolates are identical and that two of the three residues are completely conserved withinA.s.sisolates, which clearly distinguishes these from otherAeromonasstrains. We suggest that this property represents an adaptive strategy to the psychrophilic lifestyle ofA.s.s.ImportanceAeromonas salmonicidasubsp.salmonicida(A.s.s) is the causative agent of furunculosis, a bacterial septicemia of cold water fish of theSalmonidaefamily. As it has a well-defined host range,A.s.shas become an ideal model to investigate the co-evolution of host and pathogen. For many pathogens, melanin production is associated with virulence. Although other species ofAeromonascan produce melanin,A.s.sis the only member of this genus that has been reported to exhibit temperature-dependent melanization. Here we demonstrate that thermosensitive melanogenesis inA.s.sstrains is due to the thermolability of 4-hydroxyphenylpyruvate dioxygenase (HppD). The strictly conservedhppDsequences amongA.s.sand the exclusive thermosensitive pigmentation of these strains might provide insight into the role of melanin in the adaptation to a particular host, and offer a novel molecular marker to readily differentiateA.s.sstrains from otherA. salmonicidasubspecies andAeromonasspecies.

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