A Brownian Dynamics Program for the Simulation of Linear and Circular DNA and Other Wormlike Chain Polyelectrolytes

Klenin, Konstantin; Merlitz, Holger; Langowski, Jörg

doi:10.1016/s0006-3495(98)74003-2

Cited by 127 publications

(178 citation statements)

References 20 publications

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“…Recent work shows that the targeting of ATP-dependent nucleosome remodelers leads to increased mobility, suggesting that the shifting or removal of nucleosomes changes the flexibility of the chromatin fiber and, in turn, its mobility (Gehlen et al 2006;Neumann et al 2012). This is consistent with the notion that a chromosome can be modeled as a flexible polymer chain subject to random forces and tethering effects (Klenin et al 1998;Gehlen et al 2006;Rosa and Everaers 2008;Neumann et al 2012).…”

Section: Chromatin Dynamicssupporting

confidence: 73%

Structure and Function in the Budding Yeast Nucleus

2012

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Budding yeast, like other eukaryotes, carries its genetic information on chromosomes that are sequestered from other cellular constituents by a double membrane, which forms the nucleus. An elaborate molecular machinery forms large pores that span the double membrane and regulate the traffic of macromolecules into and out of the nucleus. In multicellular eukaryotes, an intermediate filament meshwork formed of lamin proteins bridges from pore to pore and helps the nucleus reform after mitosis. Yeast, however, lacks lamins, and the nuclear envelope is not disrupted during yeast mitosis. The mitotic spindle nucleates from the nucleoplasmic face of the spindle pole body, which is embedded in the nuclear envelope. Surprisingly, the kinetochores remain attached to short microtubules throughout interphase, influencing the position of centromeres in the interphase nucleus, and telomeres are found clustered in foci at the nuclear periphery. In addition to this chromosomal organization, the yeast nucleus is functionally compartmentalized to allow efficient gene expression, repression, RNA processing, genomic replication, and repair. The formation of functional subcompartments is achieved in the nucleus without intranuclear membranes and depends instead on sequence elements, protein-protein interactions, specific anchorage sites at the nuclear envelope or at pores, and long-range contacts between specific chromosomal loci, such as telomeres. Here we review the spatial organization of the budding yeast nucleus, the proteins involved in forming nuclear subcompartments, and evidence suggesting that the spatial organization of the nucleus is important for nuclear function. TABLE OF CONTENTS Abstract 107Introduction 108

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Section: Chromatin Dynamicssupporting

confidence: 73%

Structure and Function in the Budding Yeast Nucleus

2012

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“…Methods DNA Simulation. The Brownian dynamics method is based on the model proposed originally by Allison (30) and later refined by several groups (31,32). The version used in this study is close to that of Vologodskii (15).…”

Section: Discussionmentioning

confidence: 99%

Tightening of DNA knots by supercoiling facilitates their unknotting by type II DNA topoisomerases

Witz

Dietler

Stasiak

2011

Proc. Natl. Acad. Sci. U.S.A.

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Using numerical simulations, we compare properties of knotted DNA molecules that are either torsionally relaxed or supercoiled. We observe that DNA supercoiling tightens knotted portions of DNA molecules and accentuates the difference in curvature between knotted and unknotted regions. The increased curvature of knotted regions is expected to make them preferential substrates of type IIA topoisomerases because various earlier experiments have concluded that type IIA DNA topoisomerases preferentially interact with highly curved DNA regions. The supercoiling-induced tightening of DNA knots observed here shows that torsional tension in DNA may serve to expose DNA knots to the unknotting action of type IIA topoisomerases, and thus explains how these topoisomerases could maintain a low knotting equilibrium in vivo, even for long DNA molecules.Brownian dynamics | DNA topology | DNA structure | DNA configurations D uring normal cell growth, various DNA transactions are facilitated by topoisomerase-mediated passage of one DNA segment through another. These strand passages can inadvertently lead to the formation of DNA knots (1-3), which are highly deleterious for living cells if not removed efficiently (4, 5). Type IIA DNA topoisomerases can use the free energy of ATP hydrolysis (6) to decrease the knotting level significantly below the equilibrium value for DNA rings subject to random passages between colliding segments (7). This topoisomerase (topo) IIA ability has been often assumed to be a physiologically relevant mechanism ensuring efficient DNA unknotting and decatenation (7-10), but doubts on this relevance have been raised as well (11). Particularly problematic is the fact that the original study establishing that type IIA DNA topoisomerases actively unknot DNA also revealed that this ability decreases sharply with increasing DNA length. Although based on only two plasmid sizes, that study showed the generality of this length dependence for several topoisomerases (7) and, therefore, active unknotting would be doomed to be ineffective for long DNA molecules, where random passages lead to very frequent knotting (12). While trying to understand why earlier experimental studies predicted ineffectiveness of type IIA DNA topoisomerases in unknotting of long DNA molecules, we recognized that these studies were performed using torsionally relaxed DNA (7), whereas naturally occurring DNA is frequently under torsional tension (13), the best-known examples of this state being negatively supercoiled bacterial plasmids. To investigate the potential effects of torsional constraints on the activity of type IIA topoisomerases, we have performed Brownian dynamics simulations to examine how negative supercoiling affects the structure of knotted DNA molecules and whether DNA supercoiling can cause knotted regions to be recognized specifically and then unknotted by topoisomerases. We observed that DNA supercoiling results in the tightening of knots, which leads directly to an increase in curvature of the knotted regions, in turn re...

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“…35,37,38 The dsDNA molecule is represented by a finegrained bead−spring model with n p = 5 stiff bonds per persistence length, l p = 50 nm. Screened Debye−Huckel interactions are used to model the long-range electrostatics of DNA−DNA interactions, and all simulations used an ionic strength of I = 10 mM, leading to a Debye length κ −1 ≈ 3 nm and a effective chain diameter of w ≈ 16 nm.…”

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confidence: 99%

Untying Knotted DNA with Elongational Flows

Renner

Doyle

2014

ACS Macro Lett.

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We present Brownian dynamics simulations of initially knotted double-stranded DNA molecules untying in elongational flows. We show that the motions of the knots are governed by a diffusion−convection equation by deriving scalings that collapse the simulation data. When being convected, all knots displace nonaffinely, and their rates of translation along the chain are topologically dictated. We discover that torus knots "corkscrew" when driven by flow, whereas nontorus knots do not. We show that a simple mechanism can explain a coupling between this rotation and the translation of a knot, explaining observed differences in knot translation rates. These types of knots are encountered in nanoscale manipulation of DNA, occur in biology at multiple length scales (DNA to umbilical cords), and are ubiquitous in daily life (e.g., hair). These results may have a broad impact on manipulations of such knots via flows, with applications to genomic sequencing and polymer processing.K nots are commonly encountered and manipulated in everyday experiences such as tying one's shoelaces or untangling spontaneously knotted strings. 1 Formally defined only for closed rings, the topologies of "open" knots (referred to hereafter simply as knots) are often unambiguous (e.g., shoelaces and neckties) and can be closed and algorithmically defined. 2−4 At microscopic scales, chromosomal knots are modified by topoisomerases during cell division 5 and are thought to participate in gene regulation. 6 Knots are found in proteins 7,8 and viral capsid DNA,9,10 likely with yet to be fully understood functions. It has been mathematically proven that knots become asymptotically likely as the length of a polymer increases, 11 a fact that explains their ubiquity.Due to the emerging significance of knotted polymers, a growing body of simulation literature is devoted to their study. 12,13 For instance, while the topology of a ring is fixed, an open polymer can spontaneously form and untie knots. 14 The probability of forming such knots can be nonmonotonic when the polymer is confined in slits 15,16 or tubes, 17 and increasing the stiffness of a polymer can similarly influence the knotting probability in unintuitive ways. 18,19 Such knots can substantially affect the mechanical properties 20,21 and rheological behavior 22 of a polymer, and the probability of forming knots has been used to infer the effective diameter of DNA molecules. 23 Recently, simulations have shown dramatic slowing of processes wherein a knot is driven along a chain such as entropic ejection of DNA from a viral capsid 24 and the translocation of single-stranded DNA (ssDNA) 25 and polypeptides 26 through pores.Common nanofluidic experiments have led to the spontaneous formation of knots in DNA by collision with channel defects 27 or the application of moderate electric fields 28,29 during electrophoresis. More broadly, the growing library of methods to manipulate DNA molecules in nanofluidic devices has enabled fundamental research about single polymer molecules. 30,31 Th...

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A Brownian Dynamics Program for the Simulation of Linear and Circular DNA and Other Wormlike Chain Polyelectrolytes

Cited by 127 publications

References 20 publications

Structure and Function in the Budding Yeast Nucleus

Structure and Function in the Budding Yeast Nucleus

Tightening of DNA knots by supercoiling facilitates their unknotting by type II DNA topoisomerases

Untying Knotted DNA with Elongational Flows

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