scholarly journals Chromatin-loop extrusion and chromatin unknotting

2018 ◽  
Author(s):  
Dusan Racko ◽  
Fabrizio Benedetti ◽  
Dimos Goundaroulis ◽  
Andrzej Stasiak
Keyword(s):  
The State ◽  
Chromatin Loop ◽  
Genomic Distance ◽  
Dna Topoisomerases ◽  
Chromosome Conformation ◽  
Double Stranded Dna ◽  
Active Mechanism ◽  
Natural Tendency ◽  
Pass Through ◽  
Type Ii Dna Topoisomerases

ABSTRACTIt has been a puzzle how decondensed interphase chromosomes remain essentially unknotted. The natural expectation is that in the presence of type II DNA topoisomerases that permit passages of double-stranded DNA regions through each other, all chromosomes should reach the state of topological equilibrium. The topological equilibrium in highly crowded interphase chromosomes forming chromosome territories would result in formation of highly knotted chromatin fibres. However, Chromosome Conformation Capture (3C) methods revealed that the decay of contacts with the genomic distance in interphase chromosomes is practically the same as in the crumpled globule state that is formed when long polymers condense without formation of any knots. To remove knots from highly crowded chromatin, one would need an active process that should not only provide the energy to move the system from the state of topological equilibrium but also guide topoisomerase-mediated passages in such a way that knots would be efficiently unknotted instead of making the knots even more complex. We show here that the process of chromatin-loop extrusion is ideally suited to actively unknot chromatin fibres in interphase chromosomes.SIGNIFICANCE STATEMENTSimilar to earphone cables crammed into a pocket, long and crowded chromatin fibres that form chromosomes in living cells have the natural tendency to get knotted. This is exacerbated by the action of DNA topoisomerases that transiently cut some chromatin fibres and let other to pass through. Yet, the knotting frequency of chromatin fibres is very low and it has been a puzzle how this is achieved. Recently a novel active mechanism known as chromatin loop extrusion has been proposed to be involved in shaping chromosomes by forming sequential arrays of ca 1 Mb large chromatin loops. Using numerical simulations, we show here that chromatin loop extrusion is ideally suited to remove knots from chromatin fibres.

scholarly journals Chromatin Loop Extrusion and Chromatin Unknotting

Polymers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1126 ◽  
Author(s):  
Dusan Racko ◽  
Fabrizio Benedetti ◽  
Dimos Goundaroulis ◽  
Andrzej Stasiak
Keyword(s):  
The State ◽  
Coarse Grained ◽  
Chromatin Loop ◽  
Type Ii ◽  
Genomic Distance ◽  
Dna Topoisomerases ◽  
Chromosome Conformation ◽  
Double Stranded Dna ◽  
Dynamics Simulations ◽  
Type Ii Dna Topoisomerases

It has been a puzzle how decondensed interphase chromosomes remain essentially unknotted. The natural expectation is that in the presence of type II DNA topoisomerases that permit passages of double-stranded DNA regions through each other, all chromosomes should reach the state of topological equilibrium. The topological equilibrium in highly crowded interphase chromosomes forming chromosome territories would result in formation of highly knotted chromatin fibres. However, Chromosome Conformation Capture (3C) methods revealed that the decay of contact probabilities with the genomic distance in interphase chromosomes is practically the same as in the crumpled globule state that is formed when long polymers condense without formation of any knots. To remove knots from highly crowded chromatin, one would need an active process that should not only provide the energy to move the system from the state of topological equilibrium but also guide topoisomerase-mediated passages in such a way that knots would be efficiently unknotted instead of making the knots even more complex. We perform coarse-grained molecular dynamics simulations of the process of chromatin loop extrusion involving knotted and catenated chromatin fibres to check whether chromatin loop extrusion may be involved in active unknotting of chromatin fibres. Our simulations show that the process of chromatin loop extrusion is ideally suited to actively unknot, decatenate and demix chromatin fibres in interphase chromosomes.

scholarly journals TOP2B: The First Thirty Years

2018 ◽  
Vol 19 (9) ◽  
pp. 2765 ◽  
Author(s):  
Caroline Austin ◽  
Ka Lee ◽  
Rebecca Swan ◽  
Mushtaq Khazeem ◽  
Catriona Manville ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Type Ii ◽  
Dna Duplex ◽  
Topoisomerase Iiα ◽  
Dna Topoisomerase ◽  
Dna Topoisomerases ◽  
Cellular Processes ◽  
Double Stranded Dna ◽  
Type Ii Dna Topoisomerases ◽  
Strand Passage

Type II DNA topoisomerases (EC 5.99.1.3) are enzymes that catalyse topological changes in DNA in an ATP dependent manner. Strand passage reactions involve passing one double stranded DNA duplex (transported helix) through a transient enzyme-bridged break in another (gated helix). This activity is required for a range of cellular processes including transcription. Vertebrates have two isoforms: topoisomerase IIα and β. Topoisomerase IIβ was first reported in 1987. Here we review the research on DNA topoisomerase IIβ over the 30 years since its discovery.

Research on the Effect of Head Type on the Hydrodynamics of Vertical Motion Vehicle Launched by Gas Curtain

2013 ◽  
Vol 310 ◽  
pp. 218-222 ◽  
Author(s):  
Wei Cao ◽  
Hai Jun Liu ◽  
Cong Wang
Keyword(s):  
Numerical Simulation ◽  
Drag Coefficient ◽  
Vertical Motion ◽  
The State ◽  
Pass Through ◽  
Head Type

The numerical simulation was used to research the effect of different head vehicles on gas curtain and hydrodynamics in the process of underwater exiting tube and movement in water and exiting water under gas curtain launch. The two different heads of the vehicles could both smoothly pass through the narrowest place of the gas curtain and enter into the gas curtain jointed with air. Head type has little influence on the state and shape of the gas curtain and on the hydrodynamics. The drag coefficient is smallest and changes stably in the process of exiting water.

scholarly journals The General Characteristics of Extremism and Analysis of the Current State of the Fight Against Extremist Crimes

Legal Concept ◽  
2020 ◽  
pp. 13-20
Author(s):  
Svyatoslav Biryukov ◽  
Mikhail Bobovkin ◽  
Mikhail Shmatov
Keyword(s):  
The State ◽  
Law Students ◽  
Teaching Staff ◽  
General Description ◽  
Public Response ◽  
The Public ◽  
Current State ◽  
Quality Of Protection ◽  
Natural Tendency ◽  
The One

Introduction: the Constitution of the Russian Federation and other Federal laws in this country guarantee the protection of the population against crimes, including criminal attacks of extremist orientation. However, recently there has been a steady trend towards an increase in the number of committed crimes of extremist orientation, which determines the need to improve the quality of protection of individual rights, and along with them, the constitutional framework of the state, since demonstratively committed extremist crimes cause a great public response and contribute to the undermining of state power. The crime statistics show a significant increase in the number of extremist crimes; there is a natural tendency to spread the ideas of extremism among the population. Unfortunately, only some of the extremist crimes are counted as such in the official statistics. The crimes of this category are often registered without taking into account the qualifying feature – the motive of national, racial, religious hatred or enmity, and, as a result, are not considered in the group of crimes of extremism. Another reason for not fully accounting for these crimes is their latency: not all victims of such criminal actions declare this for various objective and subjective reasons. The public danger of crimes of the group in question is due, on the one hand, as usual, to their group character, and on the other hand, such illegal actions incite interethnic and other hatred, which is very harmful in the context of the efforts being made to build a civil society. Currently, the legislative bodies do not clearly pay enough attention to the organization of counteraction to extremism as an anti-social phenomenon. For example, over the past ten years, the problems of countering extremism have been resolved through the adoption of only four normative legal acts of a national nature. In this regard, the authors aim to give a general description of such a phenomenon as extremism and the state of the fight against such crimes. Methods: the methodological framework for this research is a set of methods of scientific knowledge, among which the main ones are the methods of information processing and logical analysis, synthesis, induction, deduction and generalization. Results: the authors’ content of the general characteristics of extremism and analysis of the current state of the fight against crimes of extremist orientation actualizes the problem of the need to improve the state of the theoretical base, prepare recommendations based on it, which would contribute to improving the efficiency of the state authorized bodies in the fight against various manifestations of extremism, and primarily in order to solve and investigate crimes of extremist orientation. Conclusions: the study has given the general characteristics of extremism and the analysis of the current state of the fight against extremist crimes in order to inform law students, and the teaching staff of law schools and practitioners to better understand the characteristics and dangers of this phenomenon.

scholarly journals Mechanism of topology simplification by type II DNA topoisomerases

2001 ◽  
Vol 98 (6) ◽  
pp. 3045-3049 ◽  
Author(s):  
A. V. Vologodskii ◽  
W. Zhang ◽  
V. V. Rybenkov ◽  
A. A. Podtelezhnikov ◽  
D. Subramanian ◽  
...  
Keyword(s):  
Type Ii ◽  
Dna Topoisomerases ◽  
Type Ii Dna Topoisomerases ◽  
Topology Simplification

DNA crossovers and type II DNA topoisomerases: a thermodynamical study 1 1Edited by T. Richmond

1998 ◽  
Vol 284 (5) ◽  
pp. 1279-1287 ◽  
Author(s):  
Jean-Louis Sikorav ◽  
Bertrand Duplantier ◽  
Gérard Jannink ◽  
Youri Timsit
Keyword(s):  
Type Ii ◽  
Dna Topoisomerases ◽  
Type Ii Dna Topoisomerases

The role of ATP in the reactions of type II DNA topoisomerases

2010 ◽  
Vol 38 (2) ◽  
pp. 438-442 ◽  
Author(s):  
Andrew D. Bates ◽  
Anthony Maxwell
Keyword(s):  
Atp Hydrolysis ◽  
Dna Gyrase ◽  
Dna Topology ◽  
Type Ii ◽  
Free Energies ◽  
Dna Topoisomerases ◽  
Type Ii Dna Topoisomerases ◽  
Topology Simplification ◽  
Hydrolysis Of

Type II DNA topoisomerases catalyse changes in DNA topology in reactions coupled to the hydrolysis of ATP. In the case of DNA gyrase, which can introduce supercoils into DNA, the requirement for free energy is clear. However, the non-supercoiling type II enzymes carry out reactions that are apparently energetically favourable, so their requirement for ATP hydrolysis is not so obvious. It has been shown that many of these enzymes (the type IIA family) can simplify the topology of their DNA substrates to a level beyond that expected at equilibrium. Although this seems to explain their usage of ATP, we show that the free energies involved in topology simplification are very small (<0.2% of that available from ATP) and we argue that topology simplification may simply be an evolutionary relic.

scholarly journals DiADeM: differential analysis via dependency modelling of chromatin interactions with robust generalized linear models

2019 ◽  
Author(s):  
Rafał Zaborowski ◽  
Bartek Wilczyński
Keyword(s):  
Generalized Linear Models ◽  
Linear Models ◽  
Standard Technique ◽  
Differential Analysis ◽  
Genomic Distance ◽  
Chromosome Conformation ◽  
Structure And Dynamics ◽  
Chromatin Interactions ◽  
Coverage Bias ◽  
Biochemical Technique

AbstractHigh throughput Chromosome Conformation Capture experiments have become the standard technique to assess the structure and dynamics of chromosomes in living cells. As any other sufficiently advanced biochemical technique, Hi-C datasets are complex and contain multiple documented biases, with the main ones being the non-uniform read coverage and the decay of contact coverage with genomic distance. Both of these effects have been studied and there are published methods that are able to normalize different Hi-C data to mitigate these biases to some extent. It is crucial that this is done properly, or otherwise the results of any comparative analysis of two or more Hi-C experiments are bound to be biased. In this paper we study both mentioned biases present in the Hi-C data and show that normalization techniques aimed at alleviating the coverage bias are at the same time exacerbating the problems with contact decay bias. We also postulate that it is possible to use generalized linear models to directly compare non-normalized data an that it is giving better results in identification of differential contacts between Hi-C matrices than using the normalized data.

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