Keeping intracellular DNA untangled: A new role for condensin?

Roca, Joaquím; Dyson, Sílvia; Segura, Joana; Valdés, Antonio; Martínez‐García, Belén

doi:10.1002/bies.202100187

Cited by 5 publications

(9 citation statements)

References 108 publications

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“…However, we also considered whether the activity of Topo II is regulated during G1. Specifically, yeast minichromosome experiments have shown that condensin-mediated loop extrusion biases Topo II towards disentangling minichromosomes 84,85 . Computational modeling also suggests that a mechanism of loop extrusion, by cohesin or condensin, could bias Topo II towards untangling chromosomes 83 .…”

Section: Resultsmentioning

confidence: 99%

“…Recent computational studies have proposed that loop extrusion by SMC complexes may bias Topo II towards disentanglement, or decatenation 97,98 . An elegant study in budding yeast on the topological state of yeast minichromosomes has identified a role for the condensin complex in this process 84,85 . We find that in cohesin depleted G1 cells, both compartment strength and long-range intra-chromosomal entanglement increases in a Topo II dependent manner.…”

Section: Discussionmentioning

confidence: 99%

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Mitotic chromosomes are self-entangled and disentangle through a Topoisomerase II-dependent two stage exit from mitosis

Hildebrand

Polovnikov

Dekker

et al. 2022

Preprint

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The topological state of chromosomes is an important factor controlling their mechanical properties, dynamics and function. Recent work has shown that interphase chromosomes are largely free of entanglements. How cycling cells establish this state from a dense mitotic chromosome and maintain it through interphase in the presence of Topoisomerase II activity remains mysterious. Using multi-contact 3C, Hi-C, and polymer simulations, we find that mitotic chromosomes are intrachromosomally entangled, while interphase chromosomes are not, pointing to cell cycle-dependent control of chromosome topology. The majority of mitotic entanglements are removed during anaphase/telophase, with most of the remaining ones removed during early G1, in a process that requires Topoisomerase II. Polymer simulations show that swelling and decondensation of mitotic chromosomes during mitotic exit produce entropic forces that bias Topoisomerase II activity towards decatenation of condensin loops. This is followed by prevention of formation of new entanglements by lower Topoisomerase II activity in G1, and, in heterochromatic B compartments, by interplay between cohesin and Topoisomerase II. Our results show how cells control chromosome topology during mitotic exit and G1 employing both biophysical and molecular mechanisms to modulate Topoisomerase II activity and directionality.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mitotic chromosomes are self-entangled and disentangle through a Topoisomerase II-dependent two stage exit from mitosis

Hildebrand

Polovnikov

Dekker

et al. 2022

Preprint

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“…This question is a generalization of the problem of intrachain topological entanglement, or knotting, in space-filling curves, which has bearing in biological contexts such as DNA packaging in viral capsids (46,47) and in soft matter ones related to polymers and self-assembling meta-materials in confinement (48)(49)(50)(51)(52). Extending considerations to the interlocking of self-assembled rings offers a timely reference also for challenging biological systems, such as the linked DNA ring assemblies of kinetoplasts (53) and strand crossings in DNA bundles operated by topoisomerase enzymes (44,45,54).…”

Section: Linking Probability In Space-filling Ring Meltsmentioning

confidence: 99%

Quantum-inspired encoding enhances stochastic sampling of soft matter systems

Slongo,

Hauke,

Faccioli

et al. 2023

Sci. Adv.

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Quantum advantage in solving physical problems is still hard to assess due to hardware limitations. However, algorithms designed for quantum computers may engender transformative frameworks for modeling and simulating paradigmatically hard systems. Here, we show that the quadratic unconstrained binary optimization encoding enables tackling classical many-body systems that are challenging for conventional Monte Carlo. Specifically, in self-assembled melts of rigid lattice ring polymers, the combination of high density, chain stiffness, and topological constraints results in divergent autocorrelation times for real-space Monte Carlo. Our quantum-inspired encoding overcomes this problem and enables sampling melts of lattice rings with fixed curvature and compactness, unveiling counterintuitive topological effects. Tackling the same problems with the D-Wave quantum annealer leads to substantial performance improvements and advantageous scaling of sampling computational cost with the size of the self-assembled ring melts.

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“…Cohesins cannot change any topological properties of the participating DNA domains so long as no strands are cut. But they can greatly alter their sets of accessible tertiary structures ( 121 ).…”

Section: Limitations and Opportunitiesmentioning

confidence: 99%

“…Unless prevented or resolved, they may impede essential processes such as transcription, replication and chromosome separation ( 130 , 131 ). Resolving duplex crossings that otherwise would prevent correct chromatid segregation is thought to be an important function of eukaryotic TOPO2s, perhaps aided by cohesins ( 121 ). But any action that resolves duplex crossings also would tend to untie knots and braids, and unlink catenanes.…”

Section: Topology In Biologymentioning

confidence: 99%

DNA superhelicity

Benham

2023

Nucleic Acids Research

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Closing each strand of a DNA duplex upon itself fixes its linking number L. This topological condition couples together the secondary and tertiary structures of the resulting ccDNA topoisomer, a constraint that is not present in otherwise identical nicked or linear DNAs. Fixing L has a range of structural, energetic and functional consequences. Here we consider how L having different integer values (that is, different superhelicities) affects ccDNA molecules. The approaches used are primarily theoretical, and are developed from a historical perspective. In brief, processes that either relax or increase superhelicity, or repartition what is there, may either release or require free energy. The energies involved can be substantial, sufficient to influence many events, directly or indirectly. Here two examples are developed. The changes of unconstrained superhelicity that occur during nucleosome attachment and release are examined. And a simple theoretical model of superhelically driven DNA structural transitions is described that calculates equilibrium distributions for populations of identical topoisomers. This model is used to examine how these distributions change with superhelicity and other factors, and applied to analyze several situations of biological interest.

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Keeping intracellular DNA untangled: A new role for condensin?

Cited by 5 publications

References 108 publications

Mitotic chromosomes are self-entangled and disentangle through a Topoisomerase II-dependent two stage exit from mitosis

Mitotic chromosomes are self-entangled and disentangle through a Topoisomerase II-dependent two stage exit from mitosis

Quantum-inspired encoding enhances stochastic sampling of soft matter systems

DNA superhelicity

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