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 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.

RAP-1 factor is necessary for DNA loop formation in vitro at the silent mating type locus HML

Cell ◽  
1989 ◽  
Vol 57 (5) ◽  
pp. 725-737 ◽  
Author(s):  
Johannes F.-X. Hofmann ◽  
Thierry Laroche ◽  
Andrea H. Brand ◽  
Susan M. Gasser
Keyword(s):  
Mating Type ◽  
Loop Formation ◽  
Type Locus ◽  
Mating Type Locus ◽  
Dna Loop

scholarly journals SMC complexes can traverse physical roadblocks bigger than their ring size

2021 ◽  
Author(s):  
Biswajit Pradhan ◽  
Roman Barth ◽  
Eugene Kim ◽  
Iain F. Davidson ◽  
Benedikt Bauer ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Single Molecule ◽  
Chromosome Organization ◽  
Ring Size ◽  
Single Chain ◽  
Dna Loops ◽  
Dna Loop ◽  
Covalently Linked ◽  
Structural Maintenance Of Chromosomes

The ring-shaped structural-maintenance-of-chromosomes (SMC) complexes condensin and cohesin extrude loops of DNA as a key motif in chromosome organization. It remains, however, unclear how these SMC motor proteins can extrude DNA loops in chromatin that is bound with proteins. Here, using in vitro single-molecule visualization, we show that nucleosomes, RNA polymerase, and dCas9 pose virtually no barrier to DNA loop extrusion by yeast condensin. Strikingly, we find that even DNA-bound nanoparticles as large as 200 nm, much bigger than the SMC ring size, can be translocated into DNA loops during condensin-driven extrusion. Similarly, human cohesin can pass 200 nm particles during loop extrusion, which even occurs for a single-chain version of cohesin in which the ring-forming subunits are covalently linked and cannot open up to entrap DNA. These findings disqualify all common loop-extrusion models where DNA passes through the SMC rings (pseudo)topologically, and instead point to a nontopological mechanism for DNA loop extrusion.

scholarly journals Protamine loops DNA in multiple steps

2020 ◽  
Vol 48 (11) ◽  
pp. 6108-6119
Author(s):  
Obinna A Ukogu ◽  
Adam D Smith ◽  
Luka M Devenica ◽  
Hilary Bediako ◽  
Ryan B McMillan ◽  
...  
Keyword(s):  
Radius Of Curvature ◽  
Loop Current ◽  
Dna Molecules ◽  
Loop Formation ◽  
Step Process ◽  
Force Microscopy ◽  
Atomic Force ◽  
Dna Loop ◽  
One Step

Abstract Protamine proteins dramatically condense DNA in sperm to almost crystalline packing levels. Here, we measure the first step in the in vitro pathway, the folding of DNA into a single loop. Current models for DNA loop formation are one-step, all-or-nothing models with a looped state and an unlooped state. However, when we use a Tethered Particle Motion (TPM) assay to measure the dynamic, real-time looping of DNA by protamine, we observe the presence of multiple folded states that are long-lived (∼100 s) and reversible. In addition, we measure folding on DNA molecules that are too short to form loops. This suggests that protamine is using a multi-step process to loop the DNA rather than a one-step process. To visualize the DNA structures, we used an Atomic Force Microscopy (AFM) assay. We see that some folded DNA molecules are loops with a ∼10-nm radius and some of the folded molecules are partial loops—c-shapes or s-shapes—that have a radius of curvature of ∼10 nm. Further analysis of these structures suggest that protamine is bending the DNA to achieve this curvature rather than increasing the flexibility of the DNA. We therefore conclude that protamine loops DNA in multiple steps, bending it into a loop.

scholarly journals In Silico, In Vitro, and In Vivo Estimation of J-Factors for LAC Repressor-Mediated DNA Loop Formation

2013 ◽  
Vol 104 (2) ◽  
pp. 174a-175a
Author(s):  
Sandip Kumar ◽  
David Priest ◽  
Yoav Biton ◽  
David Swigon ◽  
Keith Shearwin ◽  
...  
Keyword(s):  
In Silico ◽  
Lac Repressor ◽  
Loop Formation ◽  
Dna Loop

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 Stu2p binds tubulin and undergoes an open-to-closed conformational change

2006 ◽  
Vol 172 (7) ◽  
pp. 1009-1022 ◽  
Author(s):  
Jawdat Al-Bassam ◽  
Mark van Breugel ◽  
Stephen C. Harrison ◽  
Anthony Hyman
Keyword(s):  
Conformational Change ◽  
Conformational Transition ◽  
Budding Yeast ◽  
Microtubule Dynamics ◽  
Open Structure ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
The Common

Stu2p from budding yeast belongs to the conserved Dis1/XMAP215 family of microtubule-associated proteins (MAPs). The common feature of proteins in this family is the presence of HEAT repeat–containing TOG domains near the NH2 terminus. We have investigated the functions of the two TOG domains of Stu2p in vivo and in vitro. Our data suggest that Stu2p regulates microtubule dynamics through two separate activities. First, Stu2p binds to a single free tubulin heterodimer through its first TOG domain. A large conformational transition in homodimeric Stu2p from an open structure to a closed one accompanies the capture of a single free tubulin heterodimer. Second, Stu2p has the capacity to associate directly with microtubule ends, at least in part, through its second TOG domain. These two properties lead to the stabilization of microtubules in vivo, perhaps by the loading of tubulin dimers at microtubule ends. We suggest that this mechanism of microtubule regulation is a conserved feature of the Dis1/XMAP215 family of MAPs.

scholarly journals The impact of indole-3-lactic acid on immature intestinal innate immunity and development: a transcriptomic analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wuyang Huang ◽  
Ky Young Cho ◽  
Di Meng ◽  
W. Allan Walker
Keyword(s):  
Lactic Acid ◽  
Mechanistic Model ◽  
Transcriptomic Analysis ◽  
Dependent Manner ◽  
Protective Effects ◽  
Very Preterm Infants ◽  
Anti Inflammatory ◽  
The Impact

AbstractAn excessive intestinal inflammatory response may have a role in the pathogenesis of necrotizing enterocolitis (NEC) in very preterm infants. Indole-3-lactic acid (ILA) of breastmilk tryptophan was identified as the anti-inflammatory metabolite involved in probiotic conditioned media from Bifidobacteria longum subsp infantis. This study aimed to explore the molecular endocytic pathways involved in the protective ILA effect against inflammation. H4 cells, Caco-2 cells, C57BL/6 pup and adult mice were used to compare the anti-inflammatory mechanisms between immature and mature enterocytes in vitro and in vivo. The results show that ILA has pleiotropic protective effects on immature enterocytes including anti-inflammatory, anti-viral, and developmental regulatory potentials in a region-dependent and an age-dependent manner. Quantitative transcriptomic analysis revealed a new mechanistic model in which STAT1 pathways play an important role in IL-1β-induced inflammation and ILA has a regulatory effect on STAT1 pathways. These studies were validated by real-time RT-qPCR and STAT1 inhibitor experiments. Different protective reactions of ILA between immature and mature enterocytes indicated that ILA’s effects are developmentally regulated. These findings may be helpful in preventing NEC for premature infants.

scholarly journals Protein binding to a single termination-associated sequence in the mitochondrial DNA D-loop region.

1993 ◽  
Vol 13 (4) ◽  
pp. 2162-2171 ◽  
Author(s):  
C S Madsen ◽  
S C Ghivizzani ◽  
W W Hauswirth
Keyword(s):  
Mitochondrial Dna ◽  
Protein Binding ◽  
Loop Formation ◽  
Sequence Element ◽  
Conserved Sequence ◽  
Loop Region ◽  
In Organello ◽  
Close Proximity ◽  
D Loop

A methylation protection assay was used in a novel manner to demonstrate a specific bovine protein-mitochondrial DNA (mtDNA) interaction within the organelle (in organello). The protected domain, located near the D-loop 3' end, encompasses a conserved termination-associated sequence (TAS) element which is thought to be involved in the regulation of mtDNA synthesis. In vitro footprinting studies using a bovine mitochondrial extract and a series of deleted mtDNA templates identified a approximately 48-kDa protein which binds specifically to a single TAS element also protected within the mitochondrion. Because other TAS-like elements located in close proximity to the protected region did not footprint, protein binding appears to be highly sequence specific. The in organello and in vitro data, together, provide evidence that D-loop formation is likely to be mediated, at least in part, through a trans-acting factor binding to a conserved sequence element located 58 bp upstream of the D-loop 3' end.

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
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