scholarly journals A theory of the dynamics of DNA loop initiation in condensin/cohesin complexes

2021 ◽  
Author(s):  
Bhavin S Khatri
Keyword(s):  
Persistence Length ◽  
Diffusion Constant ◽  
Dissipation Function ◽  
Loop Formation ◽  
Parameter Uncertainties ◽  
Dna Loop ◽  
Solvent Dynamics ◽  
Current Parameter ◽  
Structural Maintenance Of Chromosome ◽  
Passage Times

The structural maintenance of chromosome complexes exhibit the remarkable ability to actively extrude DNA, which has led to the appealing and popular "loop extrusion" model to explain one of the most important processes in biology: the compaction of chromatin during the cell cycle. A potential mechanism for the action of extrusion is the classic Brownian ratchet, which requires short DNA loops to overcome an initial enthalpic barrier to bending, before favoured entropic growth of longer loops. We present a simple model of the constrained dynamics of DNA loop formation based on a frictional worm like chain, where for circular loops of order, or smaller than the persistence length, internal friction to bending dominates solvent dynamics. Using Rayleigh's dissipation function, we show how bending friction can be translated to simple one dimensional diffusion of the angle of the loop resulting in a Smoluchowski equation with a coordinate dependent diffusion constant. This interplay between Brownian motion, bending dissipation and geometry of loops leads to a qualitatively new phenomenon, where the friction vanishes for bends with an angle of exactly 180°, due to a decoupling between changes in loop curvature and angle. Using this theory and given current parameter uncertainties, we tentatively predict mean first passage times of between 1 and 10 seconds, which is of order the cycle time of ATP, suggesting spontaneous looping could be sufficient to achieve efficient initiation of looping.

scholarly journals Condensin complexes: understanding loop extrusion one conformational change at a time

2020 ◽  
Vol 48 (5) ◽  
pp. 2089-2100
Author(s):  
Erin E. Cutts ◽  
Alessandro Vannini
Keyword(s):  
Protein Structure ◽  
Recent Work ◽  
Conformational Change ◽  
Mechanistic Model ◽  
Loop Formation ◽  
Dna Loops ◽  
Dna Loop ◽  
Higher Eukaryotes ◽  
Structural Maintenance Of Chromosome

Condensin and cohesin, both members of the structural maintenance of chromosome (SMC) family, contribute to the regulation and structure of chromatin. Recent work has shown both condensin and cohesin extrude DNA loops and most likely work via a conserved mechanism. This review focuses on condensin complexes, highlighting recent in vitro work characterising DNA loop formation and protein structure. We discuss similarities between condensin and cohesin complexes to derive a possible mechanistic model, as well as discuss differences that exist between the different condensin isoforms found in higher eukaryotes.

scholarly journals Protein-Mediated DNA Loop Formation in Intrinsically Bent Substrates

2012 ◽  
Vol 102 (3) ◽  
pp. 71a
Author(s):  
Joel D. Revalee ◽  
Henry D. Wilson ◽  
Jens-Christian Meiners
Keyword(s):  
Loop Formation ◽  
Dna Loop

scholarly journals A major role for Eco1 in regulating cohesin-mediated mitotic chromosome folding

2019 ◽  
Author(s):  
Lise Dauban ◽  
Rémi Montagne ◽  
Agnès Thierry ◽  
Luciana Lazar-Stefanita ◽  
Olivier Gadal ◽  
...  
Keyword(s):  
Mitotic Chromosome ◽  
Dna Looping ◽  
Loop Formation ◽  
Dna Loops ◽  
Sister Chromatids ◽  
Topologically Associating Domains ◽  
Dna Loop ◽  
Main Barrier ◽  
Structural Maintenance Of Chromosomes ◽  
Mitotic Chromatin

AbstractUnderstanding how chromatin organizes spatially into chromatid and how sister chromatids are maintained together during mitosis is of fundamental importance in chromosome biology. Cohesin, a member of the Structural Maintenance of Chromosomes (SMC) complex family, holds sister chromatids together 1–3 and promotes long-range intra-chromatid DNA looping 4,5. These cohesin-mediated DNA loops are important for both higher-order mitotic chromatin compaction6,7 and, in some organisms, compartmentalization of chromosomes during interphase into topologically associating domains (TADs) 8,9. Our understanding of the mechanism(s) by which cohesin generates large DNA loops remains incomplete. It involves a combination of molecular partners and active expansion/extrusion of DNA loops. Here we dissect the roles on loop formation of three partners of the cohesin complex: Pds5 10, Wpl1 11 and Eco1 acetylase 12, during yeast mitosis. We identify a new function for Eco1 in negatively regulating cohesin translocase activity, which powers loop extrusion. In the absence of negative regulation, the main barrier to DNA loop expansion appears to be the centromere. Those results provide new insights on the mechanisms regulating cohesin dependent DNA looping.

DNA loop extrusion by human cohesin

Science ◽  
2019 ◽  
Vol 366 (6471) ◽  
pp. 1338-1345 ◽  
Author(s):  
Iain F. Davidson ◽  
Benedikt Bauer ◽  
Daniela Goetz ◽  
Wen Tang ◽  
Gordana Wutz ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Atpase Activity ◽  
Chromatin Structure ◽  
Adenosine Triphosphatase ◽  
Gene Recombination ◽  
Loop Formation ◽  
Base Pairs ◽  
Topologically Associating Domains ◽  
Dna Loop ◽  
Eukaryotic Genomes

Eukaryotic genomes are folded into loops and topologically associating domains, which contribute to chromatin structure, gene regulation, and gene recombination. These structures depend on cohesin, a ring-shaped DNA-entrapping adenosine triphosphatase (ATPase) complex that has been proposed to form loops by extrusion. Such an activity has been observed for condensin, which forms loops in mitosis, but not for cohesin. Using biochemical reconstitution, we found that single human cohesin complexes form DNA loops symmetrically at rates up to 2.1 kilo–base pairs per second. Loop formation and maintenance depend on cohesin’s ATPase activity and on NIPBL-MAU2, but not on topological entrapment of DNA by cohesin. During loop formation, cohesin and NIPBL-MAU2 reside at the base of loops, which indicates that they generate loops by extrusion. Our results show that cohesin and NIPBL-MAU2 form an active holoenzyme that interacts with DNA either pseudo-topologically or non-topologically to extrude genomic interphase DNA into loops.

scholarly journals Facilitation of DNA loop formation by protein–DNA non-specific interactions

Soft Matter ◽  
2019 ◽  
Vol 15 (26) ◽  
pp. 5255-5263 ◽  
Author(s):  
Jaeoh Shin ◽  
Anatoly B. Kolomeisky
Keyword(s):  
Specific Protein ◽  
Dna Looping ◽  
Specific Interactions ◽  
Loop Formation ◽  
Dna Interactions ◽  
Dna Loop ◽  
Protein Dna Interactions

DNA looping is facilitated by non-specific protein–DNA interactions.

A monte-carlo estimate of DNA loop formation

Biopolymers ◽  
1984 ◽  
Vol 23 (3) ◽  
pp. 601-605 ◽  
Author(s):  
Carol Beth Post
Keyword(s):  
Monte Carlo ◽  
Loop Formation ◽  
Monte Carlo Estimate ◽  
Dna Loop ◽  
Carlo Estimate

scholarly journals Determining the Elasticity of Short DNA Fragments using Optical Tweezers and Protein-Mediated DNA Loop Formation Assays

2013 ◽  
Vol 104 (2) ◽  
pp. 262a
Author(s):  
Alan Kandinov ◽  
Krishnan Raghunathan ◽  
Jens-Christian Meiners
Keyword(s):  
Optical Tweezers ◽  
Dna Fragments ◽  
Loop Formation ◽  
Dna Loop

scholarly journals Measurements of DNA-loop formation via Cre-mediated recombination

2012 ◽  
Vol 40 (15) ◽  
pp. 7452-7464 ◽  
Author(s):  
Massa J. Shoura ◽  
Alexandre A. Vetcher ◽  
Stefan M. Giovan ◽  
Farah Bardai ◽  
Anusha Bharadwaj ◽  
...  
Keyword(s):  
Loop Formation ◽  
Dna Loop

scholarly journals The accidental ally: Nucleosomal barriers can accelerate cohesin mediated loop formation in chromatin

2019 ◽  
Author(s):  
Ajoy Maji ◽  
Ranjith Padinhateeri ◽  
Mithun K. Mitra
Keyword(s):  
Effective Diffusion ◽  
Diffusion Constant ◽  
Loop Formation ◽  
Base Pairs ◽  
Diffusion Constants ◽  
Dna Backbone ◽  
The Mean ◽  
The Times ◽  
Lower Loop ◽  
Kinetics Of

AbstractAn important question in the context of the 3D organization of chromosomes is the mechanism of formation of large loops between distant base pairs. Recent experiments suggest that the formation of loops might be mediated by Loop Extrusion Factor proteins like cohesin. Experiments on cohesin have shown that cohesins walk diffusively on the DNA, and that nucleosomes act as obstacles to the diffusion, lowering the permeability and hence reducing the effective diffusion constant. An estimation of the times required to form the loops of typical sizes seen in Hi-C experiments using these low effective diffusion constants leads to times that are unphysically large. The puzzle then is the following, how does a cohesin molecule diffusing on the DNA backbone achieve speeds necessary to form the large loops seen in experiments? We propose a simple answer to this puzzle, and show that while at low densities, nucleosomes act as barriers to cohesin diffusion, beyond a certain concentration, they can reduce loop formation times due to a subtle interplay between the nucleosome size and the mean linker length. This effect is further enhanced on considering stochastic binding kinetics of nucleosomes on the DNA backbone, and leads to predictions of lower loop formation times than might be expected from a naive obstacle picture of nucleosomes.

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