2019
DOI: 10.1073/pnas.1815394116
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Synergy of topoisomerase and structural-maintenance-of-chromosomes proteins creates a universal pathway to simplify genome topology

Abstract: Topological entanglements severely interfere with important biological processes. For this reason, genomes must be kept unknotted and unlinked during most of a cell cycle. Type II topoisomerase (TopoII) enzymes play an important role in this process but the precise mechanisms yielding systematic disentanglement of DNA in vivo are not clear. Here we report computational evidence that structural-maintenance-of-chromosomes (SMC) proteins—such as cohesins and condensins—can cooperate with TopoII to establish a syn… Show more

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Cited by 64 publications
(52 citation statements)
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References 93 publications
(198 reference statements)
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“…Modeling chromosomes as arrays of polymer loops, we find that the compaction generated from chromosomal loop organization is capable of driving inter-chromosome disentanglement and segregation, under the conditions of fluctuating topology. Our results are complementary to, and to some extent establish a theoretical description of recent simulation results that show how loop-extruding protein machines are able to geometrically and topologically organize long polymer-like chromosomes [3][4][5].…”
supporting
confidence: 81%
See 1 more Smart Citation
“…Modeling chromosomes as arrays of polymer loops, we find that the compaction generated from chromosomal loop organization is capable of driving inter-chromosome disentanglement and segregation, under the conditions of fluctuating topology. Our results are complementary to, and to some extent establish a theoretical description of recent simulation results that show how loop-extruding protein machines are able to geometrically and topologically organize long polymer-like chromosomes [3][4][5].…”
supporting
confidence: 81%
“…We have assumed the null hypothesis of random strand passage by Topo II; a synergistic mechanism where Topo II directly interacts with SMC complexes has been suggested to drive more efficient disentanglement [5]. Intrachromosomal topology, such as chromatin knots, have also been shown to be suppressed by a combined action of SMC and Topo II [4].…”
Section: Discussionmentioning
confidence: 99%
“…Polymer simulations have shown that formation of arrays of loops during mitosis will drive segregation and decatenation of sister chromatids 32,33 . Similar extrusion processes in interphase are predicted to position linkages and crossings between and along chromosomes such that topoisomerase II action will remove these links leading to topological simplification 30,31 .…”
Section: Mc-3c Data Can Reveal Entanglements At Chromosome and Domainmentioning
confidence: 96%
“…Thus, it appears other processes must act to ensure that entanglements are prevented or are selectively removed, possibly by making topoisomerase II act not randomly so that it is directed towards disentanglement. Recent theoretical analyses have demonstrated that a process of loop formation through chromatin extrusion that strictly acts in cis will lead to a largely disentangled genome [29][30][31] . Polymer simulations have shown that formation of arrays of loops during mitosis will drive segregation and decatenation of sister chromatids 32,33 .…”
Section: Mc-3c Data Can Reveal Entanglements At Chromosome and Domainmentioning
confidence: 99%
“…Also, newer theoretical studies based on Hi-C data showed that block co-polymer nature of chromatin, where regions with the same epigenetic marks attract each other, suggested that the presence of knots is thermodynamically disfavoured, which in turn would direct DNA topoisomerase-mediated passages of chromatin fibres through each other towards unknotting (17). In addition, the process of chromatin loop extrusion could also provide a very efficient way to unknot chromatin (18,19).…”
Section: Introductionmentioning
confidence: 99%