scholarly journals Aurora B prevents chromosome arm separation defects by promoting telomere dispersion and disjunction

2015 ◽  
Vol 208 (6) ◽  
pp. 713-727 ◽  
Author(s):  
Céline Reyes ◽  
Céline Serrurier ◽  
Tiphaine Gauthier ◽  
Yannick Gachet ◽  
Sylvie Tournier
Keyword(s):  
Chromosome Segregation ◽  
Essential Role ◽  
Aurora B ◽  
Anaphase Onset ◽  
Mitotic Instability ◽  
Wide Range ◽  
Chromosome Arm ◽  
Multiple Levels ◽  
Chromatin Bridges ◽  
Kinase A

The segregation of centromeres and telomeres at mitosis is coordinated at multiple levels to prevent the formation of aneuploid cells, a phenotype frequently observed in cancer. Mitotic instability arises from chromosome segregation defects, giving rise to chromatin bridges at anaphase. Most of these defects are corrected before anaphase onset by a mechanism involving Aurora B kinase, a key regulator of mitosis in a wide range of organisms. Here, we describe a new role for Aurora B in telomere dispersion and disjunction during fission yeast mitosis. Telomere dispersion initiates in metaphase, whereas disjunction takes place in anaphase. Dispersion is promoted by the dissociation of Swi6/HP1 and cohesin Rad21 from telomeres, whereas disjunction occurs at anaphase after the phosphorylation of condensin subunit Cnd2. Strikingly, we demonstrate that deletion of Ccq1, a telomeric shelterin component, rescued cell death after Aurora inhibition by promoting the loading of condensin on chromosome arms. Our findings reveal an essential role for telomeres in chromosome arm segregation.

scholarly journals Aurora B and Condensin are dispensable for chromosome arm and telomere separation during meiosis II

2020 ◽  
Author(s):  
Julien Berthezene ◽  
Céline Reyes ◽  
Tong Li ◽  
Stéphane Coulon ◽  
Pascal Bernard ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Aurora B ◽  
Microtubule Attachment ◽  
Chromosome Arm ◽  
Mitosis And Meiosis ◽  
Chromatin Bridges ◽  
Meiosis I

ABSTRACTIn mitosis, while the importance of kinetochore-microtubule attachment has been known for many years, increasing evidence suggests that telomere dysfunctions also perturb chromosome segregation by contributing to the formation of chromatin bridges at anaphase. Recent evidence suggests that Aurora B ensures proper chromosome segregation during mitosis not only by controlling kinetochore-microtubule attachment but also by regulating telomere and chromosome arm separation. However, whether and how Aurora-B governs telomere separation during meiosis has remained unknown. Here, we show that fission yeast Aurora B localizes at telomeres during meiosis I and promotes telomere separation independently of the meiotic cohesin Rec8. In meiosis II, Aurora-B controls kinetochore-microtubule attachment but appears dispensable for telomere and chromosome arm separation. Likewise, condensin activity is nonessential in meiosis II for telomere and chromosome arm separation. Thus, in meiosis, the requirements for Aurora-B are distinct at centromeres and telomeres, illustrating the critical differences in the control of chromosome segregation between mitosis and meiosis II.

scholarly journals Differential requirement for Bub1 and Bub3 in regulation of meiotic versus mitotic chromosome segregation

2020 ◽  
Vol 219 (4) ◽  
Author(s):  
Gisela Cairo ◽  
Anne M. MacKenzie ◽  
Soni Lacefield
Keyword(s):  
Chromosome Segregation ◽  
Protein Phosphatase ◽  
Mitotic Chromosome ◽  
Budding Yeast ◽  
Meiotic Chromosome ◽  
Protein Phosphatase 1 ◽  
Aurora B ◽  
Chromosome Missegregation ◽  
Anaphase Onset ◽  
Spindle Microtubules

Accurate chromosome segregation depends on the proper attachment of kinetochores to spindle microtubules before anaphase onset. The Ipl1/Aurora B kinase corrects improper attachments by phosphorylating kinetochore components and so releasing aberrant kinetochore–microtubule interactions. The localization of Ipl1 to kinetochores in budding yeast depends upon multiple pathways, including the Bub1–Bub3 pathway. We show here that in meiosis, Bub3 is crucial for correction of attachment errors. Depletion of Bub3 results in reduced levels of kinetochore-localized Ipl1 and concomitant massive chromosome missegregation caused by incorrect chromosome–spindle attachments. Depletion of Bub3 also results in shorter metaphase I and metaphase II due to premature localization of protein phosphatase 1 (PP1) to kinetochores, which antagonizes Ipl1-mediated phosphorylation. We propose a new role for the Bub1–Bub3 pathway in maintaining the balance between kinetochore localization of Ipl1 and PP1, a balance that is essential for accurate meiotic chromosome segregation and timely anaphase onset.

scholarly journals Centromere-localized Aurora B kinase is required for the fidelity of chromosome segregation

2019 ◽  
Vol 219 (2) ◽  
Author(s):  
Cai Liang ◽  
Zhenlei Zhang ◽  
Qinfu Chen ◽  
Haiyan Yan ◽  
Miao Zhang ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Essential Role ◽  
Spindle Assembly Checkpoint ◽  
Histone H3 ◽  
Spindle Assembly ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Chromosome Missegregation ◽  
Proper Timing ◽  
Segregation Of Chromosomes

Aurora B kinase plays an essential role in chromosome bi-orientation, which is a prerequisite for equal segregation of chromosomes during mitosis. However, it remains largely unclear whether centromere-localized Aurora B is required for faithful chromosome segregation. Here we show that histone H3 Thr-3 phosphorylation (H3pT3) and H2A Thr-120 phosphorylation (H2ApT120) can independently recruit Aurora B. Disrupting H3pT3-mediated localization of Aurora B at the inner centromere impedes the decline in H2ApT120 during metaphase and causes H2ApT120-dependent accumulation of Aurora B at the kinetochore-proximal centromere. Consequently, silencing of the spindle assembly checkpoint (SAC) is delayed, whereas the fidelity of chromosome segregation is negligibly affected. Further eliminating an H2ApT120-dependent pool of Aurora B restores proper timing for SAC silencing but increases chromosome missegregation. Our data indicate that H2ApT120-mediated localization of Aurora B compensates for the loss of an H3pT3-dependent pool of Aurora B to correct improper kinetochore–microtubule attachments. This study provides important insights into how centromeric Aurora B regulates SAC and kinetochore attachment to microtubules to ensure error-free chromosome segregation.

scholarly journals Aurora B and condensin are dispensable for chromosome arm and telomere separation during meiosis II

2020 ◽  
Vol 31 (9) ◽  
pp. 889-905 ◽  
Author(s):  
Julien Berthezene ◽  
Céline Reyes ◽  
Tong Li ◽  
Stéphane Coulon ◽  
Pascal Bernard ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Aurora B ◽  
Chromosome Arm ◽  
Mitosis And Meiosis ◽  
Meiosis I

In fission yeast, Aurora B localizes at telomeres during meiosis I and promotes telomere and chromosome arm separation as observed in mitosis. Oppositely, in meiosis II, Aurora B and condensin appear dispensable for telomere and chromosome arm separation illustrating the critical differences in the control of chromosome segregation between mitosis and meiosis II.

scholarly journals A stochastic model of kinetochore–microtubule attachment accurately describes fission yeast chromosome segregation

2012 ◽  
Vol 196 (6) ◽  
pp. 757-774 ◽  
Author(s):  
Guillaume Gay ◽  
Thibault Courtheoux ◽  
Céline Reyes ◽  
Sylvie Tournier ◽  
Yannick Gachet
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Aurora B ◽  
Segregation Behavior ◽  
Microtubule Attachment ◽  
Anaphase Onset ◽  
Sister Chromatids ◽  
Yeast Chromosome ◽  
Spindle Microtubules ◽  
Early Mitosis

In fission yeast, erroneous attachments of spindle microtubules to kinetochores are frequent in early mitosis. Most are corrected before anaphase onset by a mechanism involving the protein kinase Aurora B, which destabilizes kinetochore microtubules (ktMTs) in the absence of tension between sister chromatids. In this paper, we describe a minimal mathematical model of fission yeast chromosome segregation based on the stochastic attachment and detachment of ktMTs. The model accurately reproduces the timing of correct chromosome biorientation and segregation seen in fission yeast. Prevention of attachment defects requires both appropriate kinetochore orientation and an Aurora B–like activity. The model also reproduces abnormal chromosome segregation behavior (caused by, for example, inhibition of Aurora B). It predicts that, in metaphase, merotelic attachment is prevented by a kinetochore orientation effect and corrected by an Aurora B–like activity, whereas in anaphase, it is corrected through unbalanced forces applied to the kinetochore. These unbalanced forces are sufficient to prevent aneuploidy.

scholarly journals Chromosome bi-orientation on the mitotic spindle

2005 ◽  
Vol 360 (1455) ◽  
pp. 581-589 ◽  
Author(s):  
Tomoyuki U Tanaka
Keyword(s):  
Protein Kinase ◽  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Budding Yeast ◽  
Aurora B ◽  
Cohesin Complex ◽  
Spindle Poles ◽  
Anaphase Onset ◽  
Sister Kinetochore ◽  
Dependent Mechanism

For proper chromosome segregation, sister kinetochores must attach to microtubules extending from opposite spindle poles prior to anaphase onset. This state is called sister kinetochore bi-orientation or chromosome bi-orientation. The mechanism ensuring chromosome bi-orientation lies at the heart of chromosome segregation, but is still poorly understood. Recent evidence suggests that mal-oriented kinetochore-to-pole connections are corrected in a tension-dependent mechanism. The cohesin complex and the Ipl1/Aurora B protein kinase seem to be key regulators for this correction. In this article, I discuss how cells ensure sister kinetochore bi-orientation for all chromosomes, mainly focusing on our recent findings in budding yeast.

scholarly journals The Aurora B gradient sustains kinetochore stability in anaphase

2021 ◽  
Author(s):  
Diana Papini ◽  
Mark Levasseur ◽  
Jonathan M.G. Higgins
Keyword(s):  
Chromosome Segregation ◽  
Cyclin B ◽  
Aurora B ◽  
Central Spindle ◽  
Anaphase Onset ◽  
Kinetochore Function

AbstractKinetochores assemble on chromosomes in mitosis to allow microtubules to attach and bring about accurate chromosome segregation. The kinases Cyclin B-Cdk1 and Aurora B are crucial for the formation of stable kinetochores. However, the activity of these two kinases appears to decline dramatically at centromeres during anaphase onset, precisely when microtubule attachments are required to move chromosomes towards opposite poles of the dividing cell. We find that, although Aurora B leaves centromeres at anaphase, a gradient of Aurora B activity centred on the central spindle is still able to phosphorylate kinetochore substrates such as Dsn1 to modulate kinetochore stability in anaphase and to regulate kinetochore disassembly as cells enter telophase. We provide a model to explain how Aurora B co-operates with Cyclin B-Cdk1 to maintain kinetochore function in anaphase.

scholarly journals Bub3 and Bub1 maintain the balance of kinetochore-localized Aurora B Kinase and Protein Phosphatase I to Regulate Chromosome Segregation and Anaphase Onset in Meiosis

2019 ◽  
Author(s):  
Gisela Cairo ◽  
Anne M. MacKenzie ◽  
Soni Lacefield
Keyword(s):  
Chromosome Segregation ◽  
Protein Phosphatase ◽  
Meiotic Chromosome ◽  
Protein Phosphatase 1 ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Checkpoint Proteins ◽  
Anaphase Onset ◽  
Normal Duration ◽  
Spindle Microtubules

AbstractAccurate chromosome segregation depends on proper attachment of kinetochores to spindle microtubules prior to anaphase onset. The Ipl1/Aurora B kinase corrects improper attachments by phosphorylating kinetochore components and so releasing aberrant kinetochore-microtubule interactions. The localization of Ipl1 to kinetochores in budding yeast depends upon multiple pathways, including the Bub1/Bub3 pathway. We show here that in meiosis, Bub3 is crucial for correction of attachment errors. Depletion of Bub3 results in reduced levels of kinetochore-localized Ipl1, and concomitant massive chromosome mis-segregation caused by incorrect chromosome-spindle attachments. Depletion of Bub3 also results in shorter metaphase I and metaphase II due to premature localization of protein phosphatase 1 (PP1) to kinetochores, which antagonizes Ipl1-mediated phosphorylation. We propose a new role for the Bub1-Bub3 pathway in maintaining the balance between kinetochore-localization of Ipl1 and PP1, a balance that is essential for accurate meiotic chromosome segregation and timely anaphase onset.SummaryCairo et al show that in S. cerevisiae meiosis, spindle checkpoint proteins Bub1 and Bub3 have an essential role in preventing chromosome mis-segregation and setting the normal duration of anaphase I and anaphase II onset by regulating the kinetochore-localization of Ipl1 and PP1.

scholarly journals Genetic Differentiation in Anthocyanin Content among Berry Fruits

2021 ◽  
Vol 43 (1) ◽  
pp. 36-51
Author(s):  
Alicja Ponder ◽  
Ewelina Hallmann ◽  
Martyna Kwolek ◽  
Dominika Średnicka-Tober ◽  
Renata Kazimierczak
Keyword(s):  
Essential Role ◽  
Positive Impact ◽  
Skin Pigmentation ◽  
Highbush Blueberry ◽  
Anthocyanin Content ◽  
Healthy Nutrition ◽  
Wide Range ◽  
Health Promoting ◽  
Berry Fruits ◽  
Red Currant

Anthocyanins are widely distributed secondary metabolites that play an essential role in skin pigmentation of many plant organs and microorganisms. Anthocyanins have been associated with a wide range of biological and pharmacological properties. They are also effective agents in the prevention and treatment of many chronic diseases. Berries are particularly abundant in these compounds; therefore, their dietary intake has health-promoting effects. The aim of this study was to identify and determine the anthocyanin content in selected species and cultivars of berry fruits, such as raspberry, blackberry, red currant, blackcurrant, and highbush blueberry, widely consumed by Europeans. The concentrations of anthocyanins were determined by HPLC, identifying individual compounds: cyanidin-3-O-glucoside, pelargonidin-3-O-glucoside, delphinidin-3-O-glucoside, delphinidin-3-O-rutinoside, cyanidin-3-O-rutinoside, delphinidin-3-O-galactoside, cyanidin-3-O-galactoside, and malvidin-3-O-galactoside. The experimental data showed that the selected species and cultivars of berry fruits differ significantly in the contents of anthocyanins. Among all species tested, blackberry and blackcurrant were characterized significantly by the highest content of anthocyanins (sum), while the lowest content was found in red currant fruits. Additionally, the content of individual anthocyanin compounds in particular species and cultivars was also different. Considering the high content of anthocyanins and their potential positive impact on human health and protection against disease, berries should be part of healthy nutrition.

scholarly journals A Productive Expression Platform Derived from Host-Restricted Eilat Virus: Its Extensive Validation and Novel Strategy

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 660
Author(s):  
Lu Tan ◽  
Yiwen Zhang ◽  
Xingxing Wang ◽  
Dal Young Kim
Keyword(s):  
Expression Vectors ◽  
Structural Genes ◽  
Host Restriction ◽  
Expression Platform ◽  
Mosquito Cells ◽  
Wide Range ◽  
Restriction Property ◽  
Infected Cells ◽  
Multiple Levels ◽  
Novel Strategy

Most alphaviruses are transmitted by mosquitoes and infect a wide range of insects and vertebrates. However, Eilat virus (EILV) is defective for infecting vertebrate cells at multiple levels of the viral life cycle. This host-restriction property renders EILV an attractive expression platform since it is not infectious for vertebrates and therefore provides a highly advantageous safety profile. Here, we investigated the feasibility of versatile EILV-based expression vectors. By replacing the structural genes of EILV with those of other alphaviruses, we generated seven different chimeras. These chimeras were readily rescued in the original mosquito cells and were able to reach high titers, suggesting that EILV is capable of packaging the structural proteins of different lineages. We also explored the ability of EILV to express authentic antigens via double subgenomic (SG) RNA vectors. Four foreign genetic materials of varied length were introduced into the EILV genome, and the expressed heterologous genetic materials were readily detected in the infected cells. By inserting an additional SG promoter into the chimera genome containing the structural genes of Chikungunya virus (CHIKV), we developed a bivalent vaccine candidate against CHIKV and Zika virus. These data demonstrate the outstanding compatibility of the EILV genome. The produced recombinants can be applied to vaccine and diagnostic tool development, but more investigations are required.

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