scholarly journals CENP-C is a blueprint for constitutive centromere–associated network assembly within human kinetochores

2015 ◽  
Vol 210 (1) ◽  
pp. 11-22 ◽  
Author(s):  
Kerstin Klare ◽  
John R. Weir ◽  
Federica Basilico ◽  
Tomasz Zimniak ◽  
Lucia Massimiliano ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
The Other ◽  
Microtubule Binding ◽  
Kinetochore Assembly ◽  
Binding Interface ◽  
Other Hand ◽  
Spindle Microtubules ◽  
Data Point

Kinetochores are multisubunit complexes that assemble on centromeres to bind spindle microtubules and promote faithful chromosome segregation during cell division. A 16-subunit complex named the constitutive centromere–associated network (CCAN) creates the centromere–kinetochore interface. CENP-C, a CCAN subunit, is crucial for kinetochore assembly because it links centromeres with the microtubule-binding interface of kinetochores. The role of CENP-C in CCAN organization, on the other hand, had been incompletely understood. In this paper, we combined biochemical reconstitution and cellular investigations to unveil how CENP-C promotes kinetochore targeting of other CCAN subunits. The so-called PEST domain in the N-terminal half of CENP-C interacted directly with the four-subunit CCAN subcomplex CENP-HIKM. We identified crucial determinants of this interaction whose mutation prevented kinetochore localization of CENP-HIKM and of CENP-TW, another CCAN subcomplex. When considered together with previous observations, our data point to CENP-C as a blueprint for kinetochore assembly.

scholarly journals The human Mis12 complex is required for kinetochore assembly and proper chromosome segregation

2006 ◽  
Vol 173 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Susan L. Kline ◽  
Iain M. Cheeseman ◽  
Tetsuya Hori ◽  
Tatsuo Fukagawa ◽  
Arshad Desai
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Essential Role ◽  
Stable Complex ◽  
Wild Type ◽  
Outer Plate ◽  
Checkpoint Protein ◽  
Kinetochore Assembly ◽  
Attachment Sites ◽  
Spindle Microtubules

During cell division, kinetochores form the primary chromosomal attachment sites for spindle microtubules. We previously identified a network of 10 interacting kinetochore proteins conserved between Caenorhabditis elegans and humans. In this study, we investigate three proteins in the human network (hDsn1Q9H410, hNnf1PMF1, and hNsl1DC31). Using coexpression in bacteria and fractionation of mitotic extracts, we demonstrate that these proteins form a stable complex with the conserved kinetochore component hMis12. Human or chicken cells depleted of Mis12 complex subunits are delayed in mitosis with misaligned chromosomes and defects in chromosome biorientation. Aligned chromosomes exhibited reduced centromere stretch and diminished kinetochore microtubule bundles. Consistent with this, localization of the outer plate constituent Ndc80HEC1 was severely reduced. The checkpoint protein BubR1, the fibrous corona component centromere protein (CENP) E, and the inner kinetochore proteins CENP-A and CENP-H also failed to accumulate to wild-type levels in depleted cells. These results indicate that a four-subunit Mis12 complex plays an essential role in chromosome segregation in vertebrates and contributes to mitotic kinetochore assembly.

scholarly journals The chromosomal passenger complex establishes chromosome biorientation via two parallel localization pathways

2020 ◽  
Author(s):  
Theodor Marsoner ◽  
Poornima Yedavalli ◽  
Chiara Masnovo ◽  
Katrin Schmitzer ◽  
Christopher S. Campbell
Keyword(s):  
Chromosome Segregation ◽  
Budding Yeast ◽  
Small Region ◽  
The Other ◽  
Chromosomal Passenger Complex ◽  
Microtubule Binding ◽  
Chromosome Alignment ◽  
Chromosomal Passenger ◽  
Spindle Microtubules ◽  
Do So

AbstractChromosome biorientation is established by the four-member chromosomal passenger complex (CPC) through phosphorylation of incorrect kinetochore-microtubule attachments. During chromosome alignment, the CPC localizes to the inner centromere, the inner kinetochore and spindle microtubules. Here we show that a small region of the CPC subunit INCENP/Sli15 is required to target the complex to all three of these locations in budding yeast. This region, the SAH, is essential for phosphorylation of outer kinetochore substrates, chromosome segregation, and viability. By restoring the CPC to each of these three locations individually, we found that inner centromere localization is sufficient to establish chromosome biorientation and viability independently of the other two targeting mechanisms. Remarkably, although neither the inner kinetochore nor microtubule binding activities was able to rescue viability individually, they were able to do so when combined. We have therefore identified two parallel pathways by which the CPC can promote chromosome biorientation and proper completion of mitosis.

scholarly journals The pseudo GTPase CENP-M drives human kinetochore assembly

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Federica Basilico ◽  
Stefano Maffini ◽  
John R Weir ◽  
Daniel Prumbaum ◽  
Ana M Rojas ◽  
...  
Keyword(s):  
Cell Division ◽  
Small Gtpases ◽  
Conformational Switching ◽  
Point Mutant ◽  
Kinetochore Assembly ◽  
Gtp Binding ◽  
Chromosome Alignment ◽  
Spindle Microtubules ◽  
And Function

Kinetochores, multi-subunit complexes that assemble at the interface with centromeres, bind spindle microtubules to ensure faithful delivery of chromosomes during cell division. The configuration and function of the kinetochore–centromere interface is poorly understood. We report that a protein at this interface, CENP-M, is structurally and evolutionarily related to small GTPases but is incapable of GTP-binding and conformational switching. We show that CENP-M is crucially required for the assembly and stability of a tetramer also comprising CENP-I, CENP-H, and CENP-K, the HIKM complex, which we extensively characterize through a combination of structural, biochemical, and cell biological approaches. A point mutant affecting the CENP-M/CENP-I interaction hampers kinetochore assembly and chromosome alignment and prevents kinetochore recruitment of the CENP-T/W complex, questioning a role of CENP-T/W as founder of an independent axis of kinetochore assembly. Our studies identify a single pathway having CENP-C as founder, and CENP-H/I/K/M and CENP-T/W as CENP-C-dependent followers.

Meiotic CENP-C is a shepherd: bridging the space between the centromere and the kinetochore in time and space

2020 ◽  
Vol 64 (2) ◽  
pp. 251-261
Author(s):  
Jessica E. Fellmeth ◽  
Kim S. McKim
Keyword(s):  
Chromosome Segregation ◽  
New Technologies ◽  
Early Prophase ◽  
Unique Role ◽  
Kinetochore Assembly ◽  
M Phase ◽  
In Vivo Analysis ◽  
Meiosis I

Abstract While many of the proteins involved in the mitotic centromere and kinetochore are conserved in meiosis, they often gain a novel function due to the unique needs of homolog segregation during meiosis I (MI). CENP-C is a critical component of the centromere for kinetochore assembly in mitosis. Recent work, however, has highlighted the unique features of meiotic CENP-C. Centromere establishment and stability require CENP-C loading at the centromere for CENP-A function. Pre-meiotic loading of proteins necessary for homolog recombination as well as cohesion also rely on CENP-C, as do the main scaffolding components of the kinetochore. Much of this work relies on new technologies that enable in vivo analysis of meiosis like never before. Here, we strive to highlight the unique role of this highly conserved centromere protein that loads on to centromeres prior to M-phase onset, but continues to perform critical functions through chromosome segregation. CENP-C is not merely a structural link between the centromere and the kinetochore, but also a functional one joining the processes of early prophase homolog synapsis to late metaphase kinetochore assembly and signaling.

BLOCKADE OF THE SURGE OF PROLACTIN AT PRO-OESTRUS BY ADMINISTRATION OF ANTI-OESTROGENIC SUBSTANCE, MER-25

1973 ◽  
Vol 74 (4) ◽  
pp. 769-774 ◽  
Author(s):  
Akira Yokoyama ◽  
Hiroshi Tomogane ◽  
Katuaki Ôta
Keyword(s):  
Strong Evidence ◽  
The Other ◽  
Other Hand

ABSTRACT A non-steroidal oestrogen antagonist, MER-25, was administered to cycling rats for elucidating the role of oestrogen in the surge of prolactin observed on the afternoon of pro-oestrus (POe). In animals injected with 20 mg of MER-25 intramuscularly on the afternoon (16.30 h) of the first day of dioestrus (D-1), the surge of prolactin was blocked while the level of prolactin on the afternoon of POe of these animals was significantly higher than that of the corresponding controls injected with oil. Ovulation was also blocked in these animals treated with the drug on the afternoon of D-l. On the other hand, treatment on the morning (10.30 h) of the 2nd day of dioestrus failed to prevent not only the surge of prolactin but also ovulation. These observations provide strong evidence for the view that oestrogen is responsible for the surge of prolactin on the afternoon of POe, and that the surge is accompanied by that of LH.

Covid-19 – rumours and facts in media

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 171-174
Author(s):  
Tarare Toshida ◽  
Chaple Jagruti
Keyword(s):  
Social Media ◽  
Preventive Measures ◽  
Vital Role ◽  
The Other ◽  
Sources Of Information ◽  
Other Hand ◽  
Corona Virus ◽  
The People ◽  
The World

The covid-19 resulted in broad range of spread throughout the world in which India has also became a prey of it and in this situation the means of media is extensively inϑluencing the mentality of the people. Media always played a role of loop between society and sources of information. In this epidemic also media is playing a vital role in shaping the reaction in ϑirst place for both good and ill by providing important facts regarding symptoms of Corona virus, preventive measures against the virus and also how to deal with any suspect of disease to overcome covid-19. On the other hand, there are endless people who spread endless rumours overs social media and are adversely affecting life of people but we always count on media because they provide us with valuable answers to our questions, facts and everything in need. Media always remains on top of the line when it comes to stop the out spread of rumours which are surely dangerous kind of information for society. So on our side we should react fairly and maturely to handle the situation to keep it in the favour of humanity and help government not only to ϑight this pandemic but also the info emic.

The Policy of the EEC on Concentrative Joint Ventures

1992 ◽  
Vol 5 (1) ◽  
pp. 53-67
Author(s):  
D.S. Nava
Keyword(s):  
Structural Change ◽  
Joint Ventures ◽  
The Other ◽  
Legal Instrument ◽  
Other Hand ◽  
Philip Morris ◽  
Competition Rules

The EEC Treaty contains no specific provisions for the control of concentrations. Only the competition rules. Articles 85 and 86 EEC, could be considered as possible legal instruments for regulating concentrations. The Commission has had to examine whether and to what extent these provisions could be used to this end.The Commission's view has been that Article 85 does not apply to operations resulting in structural change, as is the case of concentrations and concentrative joint ventures. Cooperative operations, such as cooperative joint ventures, on the other hand fall to be assessed under Article 85. The Philip Morris case has made this position uncertain. According to the extensive interpretation of this judgement Article 85 is now applicable to certain concentrations and thus to concentrative joint ventures.There is no such uncertainty regarding the role of Article 86 in controlling concentrative joint ventures, for the Court has established in the Continental Can case that concentrations can be caught by Article 86.With the adoption in 1989 of the Regulation on concentration control the Commission finally has a legal instrument specifically designed to regulate concentrations. However, only concentrations and concentrative joint ventures which comply with certain turnover thresholds (the so-called concentrations or concentrative joint ventures with a Community dimension) can be assessed by the Commission under the Regulation. This means that the provisions of the Regulation can not be applied to concentrative joint ventures beneath the threshold.Because of the difficulty in distinguishing concentrative operations from cooperative ones, the Commission published the Notice regarding the concentrative and cooperative operations under the Regulation on the control of concentrations.

scholarly journals Notes from the Editors

2014 ◽  
Vol 108 (2) ◽  
pp. iii-ix
Keyword(s):  
Basic Research ◽  
Decision Makers ◽  
The Other ◽  
Good Effect ◽  
Scholarly Journals ◽  
Other Hand ◽  
Relevant Work

We introduce this issue with a thought. There has been much made of the need for our discipline to be “policy relevant,” and much ridicule has been directed at the Review recently that comments how little the Review offers that is relevant for decision makers. But what does it mean to be policy relevant? Generally, scholarly journals publish the best in basic research, which hopefully can be used by those in positions of authority to good effect. This often means that there are no catchy titles, nor opinion-editorial pieces that are so often portrayed as the model of policy relevant work. In our view, the role of the Review is to expand knowledge on important scholarly questions, not only to publish work that is currently popular or somehow ordained as useful by pundits. There is certainly a place for such work, but not in the pages of the Review. On the other hand, we as the editors of the Review understand the need to make the Review accessible to as broad an audience as possible, and we have made great efforts to do just that.

The influence of concealing academic achievement on the self-esteem of adolescents with low achievement

2009 ◽  
Vol 37 (6) ◽  
pp. 805-810
Author(s):  
Baoshan Zhang ◽  
Jun-Yan Zhao ◽  
Guoliang Yu
Keyword(s):  
Academic Achievement ◽  
Social Interaction ◽  
Social Interactions ◽  
Self Esteem ◽  
Low Achievers ◽  
The Self ◽  
The Other ◽  
Other Hand ◽  
Positive Performance

An examination was carried out of the influences of concealing academic achievement on self-esteem in an academically relevant social interaction based on the assumption that concealing socially devalued characteristics should influence individuals' self-esteem during social interactions. An interview paradigm called for school-aged adolescents who either were or were not low (academic) achievers to play the role of students who were or were not low achievers while answering academically relevant questions. The data suggest that the performance self-esteem of low achievers who played the role of good students was more positive than that of low achievers who played the role of low achievers. On the other hand, participants who played the role of good students had more positive performance self-esteem than did participants who played the role of low achievers.

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