Coarse-grained modeling reveals the impact of supercoiling and loop length in DNA looping kinetics

Starr, Charles H.; Bryant, Zev; Spakowitz, Andrew J.

doi:10.1016/j.bpj.2022.04.009

Cited by 3 publications

(3 citation statements)

References 88 publications

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“…Using a scheme described in a recent study 63 , we implemented two types of structural moves to effectively sample a wide range of DNA configurations as part of the Metropolis process: local chain moves (pivot and crankshaft rotations) and full chain exchanges between neighboring replicas. For the local moves, we sampled the degree of pivot and crankshaft rotations from a uniform distribution between [−50 o ,50 o ].…”

Section: Methodsmentioning

confidence: 99%

Chromatinization modulates topoisomerase II processivity

Lee,

Wu,

Inman

et al. 2023

Nat Commun

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Type IIA topoisomerases are essential DNA processing enzymes that must robustly and reliably relax DNA torsional stress. While cellular processes constantly create varying torsional stress, how this variation impacts type IIA topoisomerase function remains obscure. Using multiple single-molecule approaches, we examined the torsional dependence of eukaryotic topoisomerase II (topo II) activity on naked DNA and chromatin. We observed that topo II is ~50-fold more processive on buckled DNA than previously estimated. We further discovered that topo II relaxes supercoiled DNA prior to plectoneme formation, but with processivity reduced by ~100-fold. This relaxation decreases with diminishing torsion, consistent with topo II capturing transient DNA loops. Topo II retains high processivity on buckled chromatin (~10,000 turns) and becomes highly processive even on chromatin under low torsional stress (~1000 turns), consistent with chromatin’s predisposition to readily form DNA crossings. This work establishes that chromatin is a major stimulant of topo II function.

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Section: Methodsmentioning

confidence: 99%

Chromatinization modulates topoisomerase II processivity

Lee,

Wu,

Inman

et al. 2023

Nat Commun

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“…Using a scheme described in a recent study 73 , we implemented two types of structural moves to effectively sample a wide range of DNA configurations as part of the Metropolis process: local chain moves (pivot 74 and crankshaft 75 rotations) and full chain exchanges between neighboring replicas 76 . For the local moves, we sampled the degree of pivot and crankshaft rotations from a uniform distribution between [-50°,50°].…”

Section: Methodsmentioning

confidence: 99%

“…We used a previously described method 73 to obtain the kinetics of DNA crossing formation from our saved DNA conformations. First, we computed the distribution of all site-to-site distance measurements R between every single pair of non-contiguous vertices of all our saved conformations.…”

Section: Methodsmentioning

confidence: 99%

Chromatinization Modulates Topoisomerase II Processivity

Lee,

Wu,

Inman

et al. 2023

Preprint

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Type IIA topoisomerases are essential DNA processing enzymes that must robustly and reliably relax DNA torsional stressin vivo. While cellular processes constantly create different degrees of torsional stress, how this stress feeds back to control type IIA topoisomerase function remains obscure. Using a suite of single-molecule approaches, we examined the torsional impact on supercoiling relaxation of both naked DNA and chromatin by eukaryotic topoisomerase II (topo II). We observed that topo II was at least ∼ 50-fold more processive on plectonemic DNA than previously estimated, capable of relaxing > 6000 turns. We further discovered that topo II could relax supercoiled DNA prior to plectoneme formation, but with a ∼100-fold reduction in processivity; strikingly, the relaxation rate in this regime decreased with diminishing torsion in a manner consistent with the capture of transient DNA loops by topo II. Chromatinization preserved the high processivity of the enzyme under high torsional stress. Interestingly, topo II was still highly processive (∼ 1000 turns) even under low torsional stress, consistent with the predisposition of chromatin to readily form DNA crossings. This work establishes that chromatin is a major stimulant of topo II function, capable of enhancing function even under low torsional stress.

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Attractive crowding effect on passive and active polymer looping kinetics

Yan,

Zhao,

Zhao

2024

The Journal of Chemical Physics

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Loop formation in complex environments is crucially important to many biological processes in life. In the present work, we adopt three-dimensional Langevin dynamics simulations to investigate passive and active polymer looping kinetics in crowded media featuring polymer–crowder attraction. We find polymers undergo a remarkable coil–globule–coil transition, highlighted by a marked change in the Flory scaling exponent of the gyration radius. Meanwhile, looping time as a function of the crowder’s volume fraction demonstrates an apparent non-monotonic alteration. A small number of crowders induce a compact structure, which largely facilitates the looping process. While a large number of crowders heavily impede end-to-end diffusion, looping kinetics is greatly inhibited. For a self-propelled chain, we find that the attractive crowding triggers an unusual activity effect on looping kinetics. Once a globular state is formed, activity takes an effort to open the chain from the compact structure, leading to an unexpected activity-induced inhibition of looping. If the chain maintains a coil state, the dominant role of activity is to enhance diffusivity and, thus, speed up looping kinetics. The novel conformational change and looping kinetics of both passive and active polymers in the presence of attractive crowding highlight a rather distinct scenario that has no analogy in a repulsive crowding counterpart. The underlying mechanism enriches our understanding of the crucial role of attractive interactions in modulating polymer structure and dynamics.

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Coarse-grained modeling reveals the impact of supercoiling and loop length in DNA looping kinetics

Cited by 3 publications

References 88 publications

Chromatinization modulates topoisomerase II processivity

Chromatinization modulates topoisomerase II processivity

Chromatinization Modulates Topoisomerase II Processivity

Attractive crowding effect on passive and active polymer looping kinetics

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