Real‐time detection of condensin‐driven
            <scp>DNA</scp>
            compaction reveals a multistep binding mechanism

Eeftens, Jorine M.; Bisht, S.; Kerssemakers, Jacob; Kschonsak, Marc; Haering, Christian H.; Dekker, Cees

doi:10.15252/embj.201797596

Cited by 74 publications

(91 citation statements)

References 44 publications

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“…4E; condensin, and Supplementary Fig. 14), consistent with the activity of condensin as a motor that compacts DNA (17). Some condensation events occurred in short bursts and caused the molecule to shorten ~1-2µm in a few seconds ( Fig.…”

Section: Resultssupporting

confidence: 73%

“…It is unclear whether this activity is also present in the other eukaryotic SMC complexes; cohesin and Smc5/6. Condensin loop extrusion activity leads to compaction of linear DNA against forces of up to 2pN in magnetic tweezers (17). We purified yeast condensin ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Single molecule studies of purified yeast condensin have shown that this SMC complex compacts DNA molecules on magnetic tweezers (17), translocates directedly along linear DNA molecules in an ATP-dependent manner (18) and forms DNA loop-like structures on surfaced-tethered, flow-stretched DNA (7). Furthermore, while purified condensin exhibits robust ATPase activity in the presence of DNA (17), purified yeast cohesin is a poor ATPase (19,20). Recent work has shown that the Scc2-Scc4 loader complex greatly stimulates cohesin's ATPase activity (19,20).…”

Section: Introductionmentioning

confidence: 99%

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A conserved activity for cohesin in bridging DNA molecules

Gutiérrez-Escribano

Newton

Llauró³

et al. 2019

Preprint

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Essential processes such as accurate chromosome segregation, regulation of gene expression and DNA repair rely on protein-mediated DNA tethering. Sister chromatid cohesion requires the SMC complex cohesin to act as a protein linker that holds replicated chromatids together (1, 2). The molecular mechanism by which cohesins hold sister chromatids has remained controversial. Here, we used a single molecule approach to visualise the activity of cohesin complexes as they hold DNA molecules. We describe a DNA bridging activity that requires ATP and is conserved from yeast to human cohesin. We show that cohesin can form two distinct classes of bridges at physiological conditions, a "permanent bridge" able to resists high force (over 80pN) and a "reversible bridge" that breaks at lower forces (5-40pN). Both classes of bridges require Scc2/Scc4 in addition to ATP. We demonstrate that bridge formation requires physical proximity of the DNA segments to be tethered and show that "permanent" cohesin bridges can move between two DNA molecules but cannot be removed from DNA when they occur in cis. This suggests that separate physical compartments in cohesin molecules are involved in the bridge. Finally, we show that cohesin tetramers, unlike condensin, cannot compact linear DNA molecules against low force, demonstrating that the core activity of cohesin tetramers is bridging DNA rather than compacting it. Our findings carry important implications for the understanding of the basic mechanisms behind cohesin-dependent establishment of sister chromatid cohesion and chromosome architecture.

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Section: Resultssupporting

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A conserved activity for cohesin in bridging DNA molecules

Gutiérrez-Escribano

Newton

Llauró³

et al. 2019

Preprint

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“…Loop extrusion has emerged as a vital mechanism underlying organization of chromosomes. SMC complexes (cohesin and condesnsins) can exert pN forces and are the prime candidates for driving the loop extrusion activity [26,27,[61][62][63][64]. In our model, extrusion of loops generates interloop repulsion that stretches the backbone; thus, loop extrusion may effectively control n, m, and α to drive chromosome compaction, and consequently, disentanglement in presence of Topo II.…”

Section: Discussionmentioning

confidence: 97%

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

Brahmachari

Marko

2019

Preprint

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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 compactionsegregation/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.

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“…We presume that in the apo state, the closed coiledcoils prevent binding of DNA to these hinge and head binding sites. A number of SMC complexes have been observed to be able to bind to DNA so as to trap small DNA loops, in the range from 70 nm to 200 nm in size (200 to 600 bp) [35][36][37][38]; this likely involves having DNA bound at two of these sites spaced appropriately to facilitate DNA distortion. These As in all molecular motor models, the cycle is driven in one direction (rather than diffusing back and forth) by the directionality of ATP binding and hydrolysis.…”

Section: Reaction Cycle For Translocation Of Smc Along Dnamentioning

confidence: 99%

DNA-segment-capture model for loop extrusion by structural maintenance of chromosome (SMC) protein complexes

Marko¹,

Rios

Barducci

et al. 2018

Preprint

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Cells possess remarkable control of the folding and entanglement topology of very long and flexible chromosomal DNA molecules. It is thought that structural maintenance of chromosome (SMC) protein complexes play a crucial role in this, by organizing long DNAs into series of loops.Recent experimental data suggest that SMC complexes are able to translocate on DNA, as well as pull out lengths of DNA via a 'loop extrusion' process. We describe a Brownian loop-captureratchet model for translocation and loop extrusion based on known structural, catalytic, and DNA-binding properties of the Bacillus subtilis SMC complex. Our model provides an example of a new class of molecular motor where large conformational fluctuations of the motor 'track' -in this case DNA -are involved in the basic translocation process. Quantitative analysis of our model leads to a series of predictions for the motor properties of SMC complexes, most strikingly a strong dependence of SMC translocation velocity on tension in the DNA track that it is moving along.

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Real‐time detection of condensin‐driven DNA compaction reveals a multistep binding mechanism

Cited by 74 publications

References 44 publications

A conserved activity for cohesin in bridging DNA molecules

A conserved activity for cohesin in bridging DNA molecules

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

DNA-segment-capture model for loop extrusion by structural maintenance of chromosome (SMC) protein complexes

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