scholarly journals Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold

2018 ◽  
Author(s):  
Mingxuan Sun ◽  
Ronald Biggs ◽  
Jessica Hornick ◽  
John F. Marko
Keyword(s):  
Large Scale ◽  
Force Measurement ◽  
Protein Complexes ◽  
Elastic Stiffness ◽  
Main Element ◽  
Mitotic Chromosomes ◽  
Metaphase Chromosomes ◽  
Fold Reduction ◽  
Subunit Expression

AbstractDuring cell division, chromosomes must be folded into their compact mitotic form to ensure their segregation. This process is thought to be largely controlled by the action of condensin SMC protein complexes on chromatin fibers. However, how condensins organize metaphase chromosomes is not understood. We have combined micromanipulation of single human mitotic chromosomes, sub-nanonewton force measurement, siRNA interference of condensin subunit expression, and fluorescence microscopy, to analyze the role of condensin in large-scale chromosome organization. Condensin depletion leads to a dramatic (~10 fold) reduction in chromosome elastic stiffness relative to the native, non-depleted case. We also find that prolonged metaphase stalling of cells leads to overloading of chromosomes with condensin, with abnormally high chromosome stiffness. These results demonstrate that condensin is a main element controlling the stiffness of mitotic chromosomes. Isolated, slightly stretched chromosomes display a discontinuous condensing staining pattern, suggesting that condensins organize mitotic chromosomes by forming isolated compaction centers that do not form a continuous scaffold.

scholarly journals Chromosome disentanglement driven via optimal compaction of loop-extruded brush structures

2019 ◽  
Vol 116 (50) ◽  
pp. 24956-24965 ◽  
Author(s):  
Sumitabha Brahmachari ◽  
John F. Marko
Keyword(s):  
Expression Patterns ◽  
Polymer Brush ◽  
Mitotic Chromosomes ◽  
Mechanical Stiffness ◽  
Structural Reorganization ◽  
Metaphase Chromosomes ◽  
Dna Topoisomerase ◽  
Topo Ii ◽  
Strand Passage

Eukaryote cell division features a chromosome compaction–decompaction cycle that is synchronized with their physical and topological segregation. It has been proposed that lengthwise compaction of chromatin into mitotic chromosomes via loop extrusion underlies the compaction-segregation/resolution process. We analyze this disentanglement scheme via considering the chromosome to be a succession of DNA/chromatin loops—a polymer “brush”—where active extrusion of loops controls the brush structure. Given type-II DNA topoisomerase (Topo II)-catalyzed topology fluctuations, we find that interchromosome entanglements are minimized for a certain “optimal” loop that scales with the chromosome size. The optimal loop organization is in accord with experimental data across species, suggesting an important structural role of genomic loops in maintaining a less entangled genome. Application of the model to the interphase genome indicates that active loop extrusion can maintain a level of chromosome compaction with suppressed entanglements; the transition to the metaphase state requires higher lengthwise compaction and drives complete topological segregation. Optimized genomic loops may provide a means for evolutionary propagation of gene-expression patterns while simultaneously maintaining a disentangled genome. We also find that compact metaphase chromosomes have a densely packed core along their cylindrical axes that explains their observed mechanical stiffness. Our model connects chromosome structural reorganization to topological resolution through the cell cycle and highlights a mechanism of directing Topo II-mediated strand passage via loop extrusion-driven lengthwise compaction.

scholarly journals Chromosome disentanglement driven via optimal compaction of loop-extruded brush structures

2019 ◽  
Author(s):  
Sumitabha Brahmachari ◽  
John F. Marko
Keyword(s):  
Expression Patterns ◽  
Polymer Brush ◽  
Chromosome Size ◽  
Mitotic Chromosomes ◽  
Mechanical Stiffness ◽  
Structural Reorganization ◽  
Metaphase Chromosomes ◽  
Topo Ii ◽  
Strand Passage

AbstractEukaryote cell division features a chromosome compaction-decompaction cycle that is synchronized with their physical and topological segregation. It has been proposed that lengthwise compaction of chromatin into mitotic chromosomes via loop extrusion underlies the compaction-segregation/resolution process. We analyze this disentanglement scheme via considering the chromosome to be a succession of DNA/chromatin loops - a polymer “brush” - where active extrusion of loops controls the brush structure. Given topoisomerase (TopoII)-catalyzed topology fluctuations, we find that inter-chromosome entanglements are minimized for a certain “optimal” loop that scales with the chromosome size. The optimal loop organization is in accord with experimental data across species, suggesting an important structural role of genomic loops in maintaining a less entangled genome. Application of the model to the interphase genome indicates that active loop extrusion can maintain a level of chromosome compaction with suppressed entanglements; the transition to the metaphase state requires higher lengthwise compaction, and drives complete topological segregation. Optimized genomic loops may provide a means for evolutionary propagation of gene-expression patterns while simultaneously maintaining a disentangled genome. We also find that compact metaphase chromosomes have a densely packed core along their cylindrical axes that explains their observed mechanical stiffness. Our model connects chromosome structural reorganization to topological resolution through the cell cycle, and highlights a mechanism of directing Topo-II mediated strand passage via loop extrusion driven lengthwise compaction.

scholarly journals The role of 3’UTR-protein complexes in the regulation of protein multifunctionality and subcellular localization

2019 ◽  
Author(s):  
Diogo M. Ribeiro ◽  
Alexis Prod’homme ◽  
Adrien Teixeira ◽  
Andreas Zanzoni ◽  
Christine Brun
Keyword(s):  
Cellular Localization ◽  
Large Scale ◽  
Protein Complexes ◽  
Interaction Networks ◽  
Human Interactome ◽  
Multifunctional Proteins ◽  
Interaction Partners ◽  
Moonlighting Proteins ◽  
Rna Interaction

AbstractMultifunctional proteins often perform their different functions when localized in different subcellular compartments. However, the mechanisms leading to their localization are largely unknown. Recently, 3’UTRs were found to regulate the cellular localization of newly synthesized proteins through the co-translational formation of 3’UTR-protein complexes. Here, we investigate the formation of 3’UTR-protein complexes involving multifunctional proteins by exploiting large-scale protein-protein and protein-RNA interaction networks. Focusing on 238 human ‘extreme multifunctional’ (EMF) proteins, we predicted 1411 3’UTR-protein complexes involving 128 EMF proteins and evaluated their role in regulating protein cellular localization and multifunctionality. Notably, we find that EMF proteins lacking localization addressing signals, yet present at both the nucleus and cell surface, often form 3’UTR-protein complexes. In addition, they provide EMF proteins with the diversity of interaction partners necessary to their multifunctionality. Archetypal moonlighting proteins are also predicted to form 3’UTR-protein complexes thereby reinforcing our findings. Finally, our results indicate that the formation of 3’UTR-protein complex may be a common phenomenon in human cells, affecting up to 20% of the proteins in the human interactome.

scholarly journals The role of 3′UTR-protein complexes in the regulation of protein multifunctionality and subcellular localization

2020 ◽  
Vol 48 (12) ◽  
pp. 6491-6502
Author(s):  
Diogo M Ribeiro ◽  
Alexis Prod’homme ◽  
Adrien Teixeira ◽  
Andreas Zanzoni ◽  
Christine Brun
Keyword(s):  
Protein Trafficking ◽  
Cellular Localization ◽  
Large Scale ◽  
Protein Complexes ◽  
Interaction Network ◽  
Multifunctional Proteins ◽  
Protein Protein Interaction ◽  
Moonlighting Proteins ◽  
Rna Interaction

Abstract Multifunctional proteins often perform their different functions when localized in different subcellular compartments. However, the mechanisms leading to their localization are largely unknown. Recently, 3′UTRs were found to regulate the cellular localization of newly synthesized proteins through the formation of 3′UTR-protein complexes. Here, we investigate the formation of 3′UTR-protein complexes involving multifunctional proteins by exploiting large-scale protein-protein and protein-RNA interaction networks. Focusing on 238 human ‘extreme multifunctional’ (EMF) proteins, we predicted 1411 3′UTR-protein complexes involving 54% of those proteins and evaluated their role in regulating protein cellular localization and multifunctionality. We find that EMF proteins lacking localization addressing signals, yet present at both the nucleus and cell surface, often form 3′UTR-protein complexes, and that the formation of these complexes could provide EMF proteins with the diversity of interaction partners necessary to their multifunctionality. Our findings are reinforced by archetypal moonlighting proteins predicted to form 3′UTR-protein complexes. Finally, the formation of 3′UTR-protein complexes that involves up to 17% of the proteins in the human protein-protein interaction network, may be a common and yet underestimated protein trafficking mechanism, particularly suited to regulate the localization of multifunctional proteins.

scholarly journals SWATH-MS co-expression profiles reveal paralogue interference in protein complex evolution

2020 ◽  
Author(s):  
Luzia Stalder ◽  
Amir Banaei-Esfahani ◽  
Rodolfo Ciuffa ◽  
Joshua L Payne ◽  
Ruedi Aebersold
Keyword(s):  
Protein Complex ◽  
Large Scale ◽  
Protein Complexes ◽  
Expression Profiles ◽  
Functional Divergence ◽  
Expression Patterns ◽  
Potential Mechanism ◽  
Evolutionary Trajectories ◽  
Pattern Distribution

AbstractUnderstanding the conservation and evolution of protein complexes is of critical value to decode their function in physiological and pathological processes. One prominent proposal posits gene duplication as a potential mechanism for protein complex evolution. In this study we take advantage of large-scale proteome expression datasets to systematically investigate the role of paralogues, and specifically self-interacting paralogues, in shaping the evolutionary trajectories of protein complexes. First, we show that protein co-expression derived from quantitative proteomic matrices is a good indicator for complex membership and is conserved across species. Second, we suggest that paralogues are commonly strongly co-expressed and that for the subset of paralogues that show diverging co-expression patterns, the divergent co-expression patterns reflect both sequence and functional divergence. Finally, on this basis, we show that homomeric paralogues known to be part of protein complexes display a unique co-expression pattern distribution, with a subset of them being highly diverging. These findings support the idea that homomeric paralogues can avoid cross-interference by diversifying their expression patterns, and corroborates the role of this mechanism as a force shaping protein complex evolution and specialization.

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.

The Role of Sense of Direction and Other Factors During Navigation in a Large-Scale, Unconstrained Environment

2013 ◽  
Author(s):  
Elisabeth J. Ploran ◽  
Ericka Rovira ◽  
James C. Thompson ◽  
Raja Parasuraman
Keyword(s):  
Large Scale ◽  
Sense Of Direction

Magnetic Properties of xCeO2•(50 − x) PbO•50B2O3 Glasses and Glass Ceramics

2017 ◽  
Vol 13 (1) ◽  
pp. 4486-4494 ◽  
Author(s):  
G.El Damrawi ◽  
F. Gharghar
Keyword(s):  
Magnetic Properties ◽  
Large Scale ◽  
Glass Ceramics ◽  
Magnetic Behavior ◽  
Crystal Formation ◽  
Dual Roles ◽  
Effective Agent ◽  
Ordered Structures ◽  
Essential Change

Cerium oxide in borate glasses of composition xCeO2·(50 − x)PbO·50B2O3 plays an important role in changing both microstructure and magnetic behaviors of the system. The structural role of CeO2 as an effective agent for cluster and crystal formation in borate network is clearly evidenced by XRD technique. Both structure and size of well-formed cerium separated clusters have an effective influence on the structural properties. The cluster aggregations are documented to be found in different range ordered structures, intermediate and long range orders are the most structures in which cerium phases are involved. The nano-sized crystallized cerium species in lead borate phase are evidenced to have magnetic behavior.  The criteria of building new specific borate phase enriched with cerium as ferrimagnetism has been found to keep the magnetization in large scale even at extremely high temperature. Treating the glass thermally or exposing it to an effective dose of ionized radiation is evidenced to have an essential change in magnetic properties. Thermal heat treatment for some of investigated materials is observed to play dual roles in the glass matrix. It can not only enhance alignment processes of the magnetic moment but also increases the capacity of the crystallite species in the magnetic phases. On the other hand, reverse processes are remarked under the effect of irradiation. The magnetization was found to be lowered, since several types of the trap centers which are regarded as defective states can be produced by effect of ionized radiation. 

The Impact of Quantitative Easing on Emerging Markets – Literature Review

e-Finanse ◽  
2018 ◽  
Vol 14 (4) ◽  
pp. 67-76
Author(s):  
Piotr Bartkiewicz
Keyword(s):  
Emerging Markets ◽  
Large Scale ◽  
Empirical Literature ◽  
Quantitative Easing ◽  
Methodological Choices ◽  
The Subject ◽  
Methodological Approaches ◽  
The Impact ◽  
Sufficient Precision

AbstractThe article presents the results of the review of the empirical literature regarding the impact of quantitative easing (QE) on emerging markets (EMs). The subject is of interest to policymakers and researchers due to the increasingly larger role of EMs in the world economy and the large-scale capital flows occurring after 2009. The review is conducted in a systematic manner and takes into consideration different methodological choices, samples and measurement issues. The paper puts the summarized results in the context of transmission channels identified in the literature. There are few distinct methodological approaches present in the literature. While there is a consensus regarding the direction of the impact of QE on EMs, its size and durability have not yet been assessed with sufficient precision. In addition, there are clear gaps in the empirical findings, not least related to relative underrepresentation of the CEE region (in particular, Poland).

Age Advantages of Emotional Experience during the COVID-19 Pandemic are Robust, but Diminished Compared to Pre-pandemic Conditions

2020 ◽  
Author(s):  
Rui Sun ◽  
Disa Sauter
Keyword(s):  
Older Adults ◽  
Large Scale ◽  
Negative Emotion ◽  
Emotional Experience ◽  
Negative Emotions ◽  
Older Individuals ◽  
Selection Strategies ◽  
Scale Test ◽  
Prolonged Stress

Getting old is generally seen as unappealing, yet aging confers considerable advantages in several psychological domains (North & Fiske, 2015). In particular, older adults are better off emotionally than younger adults, with aging associated with the so-called “age advantages,” that is, more positive and less negative emotional experiences (Carstensen et al., 2011). Although the age advantages are well established, it is less clear whether they occur under conditions of prolonged stress. In a recent study, Carstensen et al (2020) demonstrated that the age advantages persist during the COVID-19 pandemic, suggesting that older adults are able to utilise cognitive and behavioural strategies to ameliorate even sustained stress. Here, we build on Carstensen and colleagues’ work with two studies. In Study 1, we provide a large-scale test of the robustness of Carstensen and colleagues’ finding that older individuals experience more positive and less negative emotions during the COVID-19 pandemic. We measured positive and negative emotions along with age information in 23,629 participants in 63 countries in April-May 2020. In Study 2, we provide a comparison of the age advantages using representative samples collected before and during the COVID-19 pandemic. We demonstrate that older people experience less negative emotion than younger people during the prolonged stress of the COVID-19 pandemic. However, the advantage of older adults was diminished during the pandemic, pointing to a likely role of older adults use of situation selection strategies (Charles, 2010).

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