DNA-loop extruding SMC complexes can traverse one another<i>in vivo</i>

Brandão, Hugo B.; Ren, Zhenglong; Karaboja, Xheni; Mirny, Leonid A.; Wang, Xindan

doi:10.1101/2020.10.26.356329

Cited by 7 publications

(10 citation statements)

References 48 publications

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“…form Z-loops). However, this possibility requires further detailed investigation since loop extrusion with LEF traversal may lead to a variety of complicated bacterial chromosome structures in simulations and in vivo ( Brandão et al, 2020 ) and is subject to ongoing investigation ( Anchimiuk et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

The interplay between asymmetric and symmetric DNA loop extrusion

Banigan

Mirny

2020

eLife

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Chromosome compaction is essential for reliable transmission of genetic information. Experiments suggest that ∼1000-fold compaction is driven by condensin complexes that extrude chromatin loops, by progressively collecting chromatin fiber from one or both sides of the complex to form a growing loop. Theory indicates that symmetric two-sided loop extrusion can achieve such compaction, but recent single-molecule studies (Golfier et al., 2020) observed diverse dynamics of condensins that perform one-sided, symmetric two-sided, and asymmetric two-sided extrusion. We use simulations and theory to determine how these molecular properties lead to chromosome compaction. High compaction can be achieved if even a small fraction of condensins have two essential properties: a long residence time and the ability to perform two-sided (not necessarily symmetric) extrusion. In mixtures of condensins I and II, coupling two-sided extrusion and stable chromatin binding by condensin II promotes compaction. These results provide missing connections between single-molecule observations and chromosome-scale organization.

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Section: Discussionmentioning

confidence: 99%

The interplay between asymmetric and symmetric DNA loop extrusion

Banigan

Mirny

2020

eLife

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“…To explain the relatively mild impact of collisions in wild-type cells, we envisaged following scenarios: (1) the traversal of Smc complexes generating interlocking loops (Brandão et al, 2020; E. Kim et al, 2020) (2) the reversal of the translocation of one Smc complex by opposing complexes (E.…”

Section: Resultsmentioning

confidence: 99%

“…With the main parS sites being clustered in a ~60 kb region of the genome (Figure 1A), collisions are accordingly expected to be rare (with or without traversal). Occasional loading of Smc at one of the more distal parS sites however would quite often lead to collisions, thus resulting in contact maps with an arc-shaped pattern, such as observed for −304kb parS (the strongest of the distal parS sites) (Figure 1C), (Brandão et al, 2020). When strong parS sites are artificially moved further away from each other, then impacts from collisions also become obvious (Figure 3).…”

Section: Discussionmentioning

confidence: 97%

“…It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in be rare (with or without traversal). Occasional loading of Smc at one of the more distal parS sites however would quite often lead to collisions, thus resulting in contact maps with an arcshaped pattern, such as observed for -304kb parS (the strongest of the distal parS sites) ( Figure 1C), (Brandão et al, 2020). When strong parS sites are artificially moved further away from each other, then impacts from collisions also become obvious (Figure 3 The presence of multiple types of SMC complexes acting on the same chromosome likely aggravates the issue of collisions.…”

Section: Avoiding Smc Encountersmentioning

confidence: 99%

“…CC-BY 4.0 International license perpetuity. It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in To explain the relatively mild impact of collisions in wild-type cells, we envisaged following scenarios: (1) the traversal of Smc complexes generating interlocking loops (Brandão et al, 2020;E. Kim et al, 2020) (2) the reversal of the translocation of one Smc complex by opposing complexes (E. Kim et al, 2020), (3) the unloading of one or both complexes upon collision, or (4) collision avoidance either by infrequent loading ( Figure 3D) or (5) by mutually exclusive parS usage ( Figure S3A).…”

Section: An Arm-modified Smc Protein Over-accumulates In the Replicatmentioning

confidence: 99%

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Fine-tuning of the Smc flux facilitates chromosome organization inB. subtilis

Anchimiuk

Lioy

Minnen

et al. 2020

Preprint

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SMC complexes are widely conserved ATP-powered loop extrusion motors indispensable for the faithful segregation of chromosomes during cell division. How SMC complexes translocate along DNA for loop extrusion and what happens when two complexes meet on the same DNA molecule is largely unknown. Revealing the origins and the consequences of SMC encounters is crucial for understanding the folding process not only of bacterial, but also of eukaryotic chromosomes. Here, we uncover several factors that influence bacterial chromosome organization by modulating the probability of such clashes. These factors include the number, the strength and the distribution of Smc loading sites, the residence time on the chromosome, the translocation rate, and the cellular abundance of Smc complexes. By studying various mutants, we show that these parameters are fine-tuned to reduce the frequency of encounters between Smc complexes, presumably as a risk mitigation strategy. Mild perturbations hamper chromosome organization by causing Smc collisions, implying that the cellular capacity to resolve them is rather limited. Altogether, we identify mechanisms that help to avoid Smc collisions and their resolution by Smc traversal or other potentially risky molecular transactions.

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DNA tension-modulated translocation and loop extrusion by SMC complexes revealed by molecular dynamics simulations

Nomidis

Carlon

Gruber

et al. 2021

Preprint

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Structural Maintenance of Chromosomes (SMC) protein complexes play essential roles in genome folding and organization across all domains of life. In order to determine how the activities of these large (about 50 nm) complexes are controlled by ATP binding and hydrolysis, we have developed a molecular dynamics (MD) model that realistically accounts for thermal conformational motions of SMC and DNA. The model SMCs make use of DNA flexibility and looping, together with an ATP-induced "power stroke", to capture and transport DNA segments, so as to robustly translocate along DNA. This process is sensitive to DNA tension: at low tension (about 0.1 pN), the model performs steps of roughly 60 nm size, while, at higher tension, a distinct inchworm-like translocation mode appears, with steps that depend on SMC arm flexibility. By permanently tethering DNA to an experimentally-observed additional binding site ("safety belt"), the same model performs loop extrusion. We find that the dependence of loop extrusion on DNA tension is remarkably different when DNA tension is fixed vs when DNA end points are fixed: Loop extrusion reversal occurs above 0.5 pN for fixed tension, while loop extrusion stalling without reversal occurs at about 2 pN for fixed end points. Our model quantitatively matches recent experimental results on condensin and cohesin, and makes a number of clear predictions. Finally we investigate how specific structural changes affect the SMC function, which is testable in experiments on varied or mutant SMCs.

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DNA-loop extruding SMC complexes can traverse one anotherin vivo

Cited by 7 publications

References 48 publications

The interplay between asymmetric and symmetric DNA loop extrusion

The interplay between asymmetric and symmetric DNA loop extrusion

Fine-tuning of the Smc flux facilitates chromosome organization inB. subtilis

DNA tension-modulated translocation and loop extrusion by SMC complexes revealed by molecular dynamics simulations

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