478 results match your criteria dna catenanes

DNA-Topology Simplification by Topoisomerases.

Molecules 2021 Jun 3;26(11). Epub 2021 Jun 3.

Department of Bioengineering, University of Texas at Dallas, 800 W Campbell Road, Richardson, TX 75080, USA.

The topological properties of DNA molecules, supercoiling, knotting, and catenation, are intimately connected with essential biological processes, such as gene expression, replication, recombination, and chromosome segregation. Non-trivial DNA topologies present challenges to the molecular machines that process and maintain genomic information, for example, by creating unwanted DNA entanglements. At the same time, topological distortion can facilitate DNA-sequence recognition through localized duplex unwinding and longer-range loop-mediated interactions between the DNA sequences. Read More

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Diversity and Functions of Type II Topoisomerases.

Acta Naturae 2021 Jan-Mar;13(1):59-75

Institute of Gene Biology RAS, Moscow, 119334 Russia.

The DNA double helix provides a simple and elegant way to store and copy genetic information. However, the processes requiring the DNA helix strands separation, such as transcription and replication, induce a topological side-effect - supercoiling of the molecule. Topoisomerases comprise a specific group of enzymes that disentangle the topological challenges associated with DNA supercoiling. Read More

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What makes a type IIA topoisomerase a gyrase or a Topo IV?

Nucleic Acids Res 2021 06;49(11):6027-6042

University of Muenster, Institute for Physical Chemistry, Corrensstrasse 30, 48149 Muenster, Germany.

Type IIA topoisomerases catalyze a variety of different reactions: eukaryotic topoisomerase II relaxes DNA in an ATP-dependent reaction, whereas the bacterial representatives gyrase and topoisomerase IV (Topo IV) preferentially introduce negative supercoils into DNA (gyrase) or decatenate DNA (Topo IV). Gyrase and Topo IV perform separate, dedicated tasks during replication: gyrase removes positive supercoils in front, Topo IV removes pre-catenanes behind the replication fork. Despite their well-separated cellular functions, gyrase and Topo IV have an overlapping activity spectrum: gyrase is also able to catalyze DNA decatenation, although less efficiently than Topo IV. Read More

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Changes in the topology of DNA replication intermediates: Important discrepancies between in vitro and in vivo.

Bioessays 2021 05 25;43(5):e2000309. Epub 2021 Feb 25.

Directorate of Research and Postgraduate Studies, Polytechnic School, National University of Asunción, P, San Lorenzo, Paraguay.

The topology of DNA duplexes changes during replication and also after deproteinization in vitro. Here we describe these changes and then discuss for the first time how the distribution of superhelical stress affects the DNA topology of replication intermediates, taking into account the progression of replication forks. The high processivity of Topo IV to relax the left-handed (+) supercoiling that transiently accumulates ahead of the forks is not essential, since DNA gyrase and swiveling of the forks cooperate with Topo IV to accomplish this task in vivo. Read More

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Purified Smc5/6 Complex Exhibits DNA Substrate Recognition and Compaction.

Mol Cell 2020 12 9;80(6):1039-1054.e6. Epub 2020 Dec 9.

Cell Cycle Group, MRC London Institute of Medical Sciences (LMS), Du Cane Road, London W12 0NN, UK. Electronic address:

Eukaryotic SMC complexes, cohesin, condensin, and Smc5/6, use ATP hydrolysis to power a plethora of functions requiring organization and restructuring of eukaryotic chromosomes in interphase and during mitosis. The Smc5/6 mechanism of action and its activity on DNA are largely unknown. Here we purified the budding yeast Smc5/6 holocomplex and characterized its core biochemical and biophysical activities. Read More

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December 2020

Hydrodynamic interactions in topologically linked ring polymers.

Phys Rev E 2020 Sep;102(3-1):032502

Pritzker School of Molecular Engineering, University of Chicago, Chicago, Illinois 60637, USA.

Despite decades of interdisciplinary research on topologically linked ring polymers, their dynamics remain largely unstudied. These systems represent a major scientific challenge as they are often subject to both topological and hydrodynamic interactions (HI), which render dynamical solutions either mathematically intractable or computationally prohibitive. Here we circumvent these limitations by preaveraging the HI of linked rings. Read More

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September 2020

Trapped topoisomerase II initiates formation of de novo duplications via the nonhomologous end-joining pathway in yeast.

Proc Natl Acad Sci U S A 2020 10 12;117(43):26876-26884. Epub 2020 Oct 12.

Pharmaceutical Sciences Department, University of Illinois at Chicago, Rockford, IL 61107;

Topoisomerase II (Top2) is an essential enzyme that resolves catenanes between sister chromatids as well as supercoils associated with the over- or under-winding of duplex DNA. Top2 alters DNA topology by making a double-strand break (DSB) in DNA and passing an intact duplex through the break. Each component monomer of the Top2 homodimer nicks one of the DNA strands and forms a covalent phosphotyrosyl bond with the 5' end. Read More

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October 2020

A novel decatenation assay for DNA topoisomerases using a singly-linked catenated substrate.

Biotechniques 2020 11 1;69(5):356-362. Epub 2020 Oct 1.

Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.

Decatenation is a crucial reaction of DNA topoisomerases in DNA replication and is frequently used in drug screening. Usually this reaction is monitored using kinetoplast DNA as a substrate, although this assay has several limitations. Here we have engineered a substrate for Tn resolvase that generates a singly-linked catenane that can readily be purified from the DNA substrate after restriction enzyme digestion and centrifugation. Read More

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November 2020

Regeneration of Burnt Bridges on a DNA Catenane Walker.

Angew Chem Int Ed Engl 2020 09 20;59(38):16366-16370. Epub 2020 Jul 20.

LIMES Chemical Biology Unit, Universität Bonn, Gerhard-Domagk-Straße 1, 53121, Bonn, Germany.

DNA walkers are molecular machines that can move with high precision onthe nanoscale due to their structural and functional programmability. Despite recent advances in the field that allow exploring different energy sources, stimuli, and mechanisms of action for these nanomachines, the continuous operation and reusability of DNA walkers remains challenging because in most cases the steps, once taken by the walker, cannot be taken again. Herein we report the path regeneration of a burnt-bridges DNA catenane walker using RNase A. Read More

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September 2020

Prokaryotic Argonautes Function beyond Immunity by Unlinking Replicating Chromosomes.

Daan C Swarts

Cell 2020 09;182(6):1381-1383

Laboratory of Biochemistry, Wageningen University and Research, Wageningen, the Netherlands. Electronic address:

Eukaryotic Argonaute proteins strictly mediate RNA-guided RNA interference. In contrast, prokaryotic Argonautes can utilize DNA guides to target complementary DNA sequences to protect their hosts against invading DNA. In this issue of Cell, Jolly and colleagues demonstrate that Thermus thermophilus Argonaute additionally participates in DNA replication by unlinking catenated chromosomes. Read More

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September 2020

Multi-contact 3C reveals that the human genome during interphase is largely not entangled.

Nat Struct Mol Biol 2020 12 14;27(12):1105-1114. Epub 2020 Sep 14.

Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.

During interphase, the eukaryotic genome is organized into chromosome territories that are spatially segregated into compartment domains. The extent to which interacting domains or chromosomes are entangled is not known. We analyze series of co-occurring chromatin interactions using multi-contact 3C (MC-3C) in human cells to provide insights into the topological entanglement of chromatin. Read More

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December 2020

Novel organization of mitochondrial minicircles and guide RNAs in the zoonotic pathogen Trypanosoma lewisi.

Nucleic Acids Res 2020 09;48(17):9747-9761

Center for Parasitic Organisms, State Key Laboratory of Biocontrol, School of Life Sciences, and Key Laboratory of Tropical Diseases Control of the Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510275, The People's Republic of China.

Kinetoplastid flagellates are known for several unusual features, one of which is their complex mitochondrial genome, known as kinetoplast (k) DNA, composed of mutually catenated maxi- and minicircles. Trypanosoma lewisi is a member of the Stercorarian group of trypanosomes which is, based on human infections and experimental data, now considered a zoonotic pathogen. By assembling a total of 58 minicircle classes, which fall into two distinct categories, we describe a novel type of kDNA organization in T. Read More

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September 2020

Thermus thermophilus Argonaute Functions in the Completion of DNA Replication.

Cell 2020 09 25;182(6):1545-1559.e18. Epub 2020 Aug 25.

Howard Hughes Medical Institute and RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address:

In many eukaryotes, Argonaute proteins, guided by short RNA sequences, defend cells against transposons and viruses. In the eubacterium Thermus thermophilus, the DNA-guided Argonaute TtAgo defends against transformation by DNA plasmids. Here, we report that TtAgo also participates in DNA replication. Read More

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September 2020

Anaphase Bridges: Not All Natural Fibers Are Healthy.

Genes (Basel) 2020 08 7;11(8). Epub 2020 Aug 7.

Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy.

At each round of cell division, the DNA must be correctly duplicated and distributed between the two daughter cells to maintain genome identity. In order to achieve proper chromosome replication and segregation, sister chromatids must be recognized as such and kept together until their separation. This process of cohesion is mainly achieved through proteinaceous linkages of cohesin complexes, which are loaded on the sister chromatids as they are generated during S phase. Read More

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Post-replicative pairing of sister ter regions in Escherichia coli involves multiple activities of MatP.

Nat Commun 2020 07 30;11(1):3796. Epub 2020 Jul 30.

Centre de Biologie Intégrative de Toulouse (CBI Toulouse), Laboratoire de Microbiologie et de Génétique Moléculaires (LMGM), Université de Toulouse, CNRS, UPS, Toulouse, France.

The ter region of the bacterial chromosome, where replication terminates, is the last to be segregated before cell division in Escherichia coli. Delayed segregation is controlled by the MatP protein, which binds to specific sites (matS) within ter, and interacts with other proteins such as ZapB. Here, we investigate the role of MatP by combining short-time mobility analyses of the ter locus with biochemical approaches. Read More

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Interlocked DNA Nanojoints for Reversible Thermal Sensing.

Angew Chem Int Ed Engl 2020 07 1;59(30):12455-12459. Epub 2020 Jul 1.

LIMES Chemical Biology Unit, Universität Bonn, Gerhard-Domagk-Straße 1, 53121, Bonn, Germany.

The ability to precisely measure and monitor temperature at high resolution at the nanoscale is an important task for better understanding the thermodynamic properties of functional entities at the nanoscale in complex systems, or at the level of a single cell. However, the development of high-resolution and robust thermal nanosensors is challenging. The design, assembly, and characterization of a group of thermal-responsive deoxyribonucleic acid (DNA) joints, consisting of two interlocked double-stranded DNA (dsDNA) rings, is described. Read More

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Topoisomerase IIα prevents ultrafine anaphase bridges by two mechanisms.

Open Biol 2020 05 13;10(5):190259. Epub 2020 May 13.

Institut Curie, PSL Research University, UMR 3348, Centre de Recherche, Orsay, France.

Topoisomerase IIα (Topo IIα), a well-conserved double-stranded DNA (dsDNA)-specific decatenase, processes dsDNA catenanes resulting from DNA replication during mitosis. Topo IIα defects lead to an accumulation of ultrafine anaphase bridges (UFBs), a type of chromosome non-disjunction. Topo IIα has been reported to resolve DNA anaphase threads, possibly accounting for the increase in UFB frequency upon Topo IIα inhibition. Read More

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Fluorescent aptasensors for parallel analysis of biomolecules based on interlocked DNA catenane nanomachines.

Anal Chim Acta 2020 Jun 6;1114:1-6. Epub 2020 Apr 6.

School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, China. Electronic address:

Stimuli-responsive DNA catenane nanomachines have received considerable interest in the area of DNA nanotechnology. However, the sensing and bio-sensing applications of DNA catenane nanomachines are rarely explored. Herein, the biological small molecule and protein responsive DNA catenane nanomachines were designed by utilizing the specific aptamer/target interaction. Read More

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MCPH1 Lack of Function Enhances Mitotic Cell Sensitivity Caused by Catalytic Inhibitors of Topo II.

Genes (Basel) 2020 04 8;11(4). Epub 2020 Apr 8.

Department of Experimental Biology, University of Jaén, 23071 Jaén, Spain.

The capacity of Topoisomerase II (Topo II) to remove DNA catenations that arise after replication is essential to ensure faithful chromosome segregation. Topo II activity is monitored during G2 by a specific checkpoint pathway that delays entry into mitosis until the chromosomes are properly decatenated. Recently, we demonstrated that the mitotic defects that are characteristic of cells depleted of MCPH1 function, a protein mutated in primary microcephaly, are not a consequence of a weakened G2 decatenation checkpoint response. Read More

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Distribution of torsional stress between the un-replicated and replicated regions in partially replicated molecules.

J Biomol Struct Dyn 2021 Apr 10;39(6):2266-2277. Epub 2020 Apr 10.

Polytechnic School, National University of Asunción, San Lorenzo, Paraguay.

DNA topology changes continuously as replication proceeds. Unwinding of the DNA duplex by helicases is favored by negative supercoiling but it causes the progressive accumulation of positive supercoiling ahead of the fork. This torsional stress must be removed for the fork to keep advancing. Read More

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Excision repair of topoisomerase DNA-protein crosslinks (TOP-DPC).

DNA Repair (Amst) 2020 05 7;89:102837. Epub 2020 Mar 7.

Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States. Electronic address:

Topoisomerases are essential enzymes solving DNA topological problems such as supercoils, knots and catenanes that arise from replication, transcription, chromatin remodeling and other nucleic acid metabolic processes. They are also the targets of widely used anticancer drugs (e.g. Read More

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Facile Characterization of Topology of DNA Catenanes.

Biophys J 2020 04 15;118(7):1702-1708. Epub 2020 Feb 15.

College of Food Science and Engineering, Ocean University of China, Nucleic acids Chemistry and Biotechnology Laboratory, Shinan-qu, Qingdao, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China. Electronic address:

During the preparation of single-stranded DNA catenanes, topological isomers of different linking numbers (Lk) are intrinsically produced, and they must be separated from each other to construct sophisticated nanostructures accurately. In many previous studies, however, mixtures of these isomers were directly employed to construct nanostructures without sufficient characterization. Here, we present a method that easily and clearly characterizes the isomers by polyacrylamide gel electrophoresis. Read More

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A DNA polymerization-independent role for mitochondrial DNA polymerase I-like protein C in African trypanosomes.

J Cell Sci 2020 05 7;133(9). Epub 2020 May 7.

Department of Microbiology, University of Massachusetts, Amherst, MA 01003, USA

Mitochondrial DNA of and related parasites is a catenated network containing thousands of minicircles and tens of maxicircles, called kinetoplast DNA (kDNA). Replication of a single nucleoid requires at least three DNA polymerase I-like proteins (i.e. Read More

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Using Two-Dimensional Intact Mitochondrial DNA (mtDNA) Agarose Gel Electrophoresis (2D-IMAGE) to Detect Changes in Topology Associated with Mitochondrial Replication, Transcription, and Damage.

Methods Mol Biol 2020 ;2119:25-42

Division of Cardiology, Department of Medicine, Center for Metabolism and Mitochondrial Medicine and the Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.

The study of mitochondrial DNA (mtDNA) integrity and how replication, transcription, repair, and degradation maintain mitochondrial function has been hampered due to the inability to identify mtDNA structural forms. Here we describe the use of 2D intact mtDNA agarose gel electrophoresis, or 2D-IMAGE, to identify up to 25 major mtDNA topoisomers such as double-stranded circular mtDNA (including supercoiled molecules, nicked circles, and multiple catenated species) and various forms containing single-stranded DNA (ssDNA) structures. Using this modification of a classical 1D gel electrophoresis procedure, many of the identified mtDNA species have been associated with mitochondrial replication, damage, deletions, and possibly transcription. Read More

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October 2020

Identification of hemicatenane-specific binding proteins by fractionation of HeLa nuclei extracts.

Biochem J 2020 01;477(2):509-524

Genome Structure and Instability Laboratory, Life Adaptations Department, CNRS UMR 7196, INSERM U1154, National Museum of Natural History, F-75005 Paris, France.

DNA hemicatenanes (HCs) are four-way junctions in which one strand of a double-stranded helix is catenated with one strand of another double-stranded DNA. Frequently mentioned as DNA replication, recombination and repair intermediates, they have been proposed to participate in the spatial organization of chromosomes and in the regulation of gene expression. To explore potential roles of HCs in genome metabolism, we sought to purify proteins capable of binding specifically HCs by fractionating nuclear extracts from HeLa cells. Read More

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January 2020

DNA Origami Catenanes Templated by Gold Nanoparticles.

Small 2020 02 9;16(6):e1905987. Epub 2020 Jan 9.

Max-Planck-Institute for Intelligent Systems, Heisenbergstr. 3, 70569, Stuttgart, Germany.

Mechanically interlocked molecules have marked a breakthrough in the field of topological chemistry and boosted the vigorous development of molecular machinery. As an archetypal example of the interlocked molecules, catenanes comprise macrocycles that are threaded through one another like links in a chain. Inspired by the transition metal-templated approach of catenanes synthesis, the hierarchical assembly of DNA origami catenanes templated by gold nanoparticles is demonstrated in this work. Read More

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February 2020

Equilibrium structure and deformation response of 2D kinetoplast sheets.

Proc Natl Acad Sci U S A 2020 01 6;117(1):121-127. Epub 2019 Dec 6.

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142;

The considerable interest in two-dimensional (2D) materials and complex molecular topologies calls for a robust experimental system for single-molecule studies. In this work, we study the equilibrium properties and deformation response of a complex DNA structure called a kinetoplast, a 2D network of thousands of linked rings akin to molecular chainmail. Examined in good solvent conditions, kinetoplasts appear as a wrinkled hemispherical sheet. Read More

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January 2020

Histone H2A phosphorylation recruits topoisomerase IIα to centromeres to safeguard genomic stability.

EMBO J 2020 02 26;39(3):e101863. Epub 2019 Nov 26.

MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China.

Chromosome segregation in mitosis requires the removal of catenation between sister chromatids. Timely decatenation of sister DNAs at mitotic centromeres by topoisomerase IIα (TOP2A) is crucial to maintain genomic stability. The chromatin factors that recruit TOP2A to centromeres during mitosis remain unknown. Read More

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February 2020

Mitochondrial Genomes: Maxicircle Structure and Heterogeneity of Minicircles.

Genes (Basel) 2019 09 26;10(10). Epub 2019 Sep 26.

Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Campus de Excelencia Internacional (CEI) UAM+CSIC, Universidad Autónoma de Madrid, 28049 Madrid, Spain.

The mitochondrial DNA (mtDNA), which is present in almost all eukaryotic organisms, is a useful marker for phylogenetic studies due to its relative high conservation and its inheritance manner. In and other trypanosomatids, the mtDNA (also referred to as kinetoplast DNA or kDNA) is composed of thousands of minicircles and a few maxicircles, catenated together into a complex network. Maxicircles are functionally similar to other eukaryotic mtDNAs, whereas minicircles are involved in RNA editing of some maxicircle-encoded transcripts. Read More

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September 2019

Design, assembly, characterization, and operation of double-stranded interlocked DNA nanostructures.

Nat Protoc 2019 10 11;14(10):2818-2855. Epub 2019 Sep 11.

Chemical Biology and Medicinal Chemistry Unit, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.

Mechanically interlocked DNA nanostructures are useful as flexible entities for operating DNA-based nanomachines. Interlocked structures made of double-stranded (ds) DNA components can be constructed by irreversibly threading them through one another to mechanically link them. The interlocked components thus remain bound to one another while still permitting large-amplitude motion about the mechanical bond. Read More

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October 2019