scholarly journals The many lives of type IA topoisomerases

2020 ◽  
Vol 295 (20) ◽  
pp. 7138-7153 ◽  
Author(s):  
Anna H. Bizard ◽  
Ian D. Hickson
Keyword(s):  
Double Helix ◽  
Helical Structure ◽  
Dna Topoisomerases ◽  
Double Helical Structure ◽  
Processing Enzymes ◽  
Type Ia ◽  
Cellular Machinery ◽  
The Many ◽  
Dna Double Helix ◽  
Dna Topoisomerase Iii

The double-helical structure of genomic DNA is both elegant and functional in that it serves both to protect vulnerable DNA bases and to facilitate DNA replication and compaction. However, these design advantages come at the cost of having to evolve and maintain a cellular machinery that can manipulate a long polymeric molecule that readily becomes topologically entangled whenever it has to be opened for translation, replication, or repair. If such a machinery fails to eliminate detrimental topological entanglements, utilization of the information stored in the DNA double helix is compromised. As a consequence, the use of B-form DNA as the carrier of genetic information must have co-evolved with a means to manipulate its complex topology. This duty is performed by DNA topoisomerases, which therefore are, unsurprisingly, ubiquitous in all kingdoms of life. In this review, we focus on how DNA topoisomerases catalyze their impressive range of DNA-conjuring tricks, with a particular emphasis on DNA topoisomerase III (TOP3). Once thought to be the most unremarkable of topoisomerases, the many lives of these type IA topoisomerases are now being progressively revealed. This research interest is driven by a realization that their substrate versatility and their ability to engage in intimate collaborations with translocases and other DNA-processing enzymes are far more extensive and impressive than was thought hitherto. This, coupled with the recent associations of TOP3s with developmental and neurological pathologies in humans, is clearly making us reconsider their undeserved reputation as being unexceptional enzymes.

DNA: Not Merely the Secret of Life

2010 ◽  
Author(s):  
Nadrian C. Seeman
Keyword(s):  
Double Helix ◽  
Genetic Material ◽  
Helical Structure ◽  
Prominent Feature ◽  
Base Pairing ◽  
Double Helical Structure ◽  
Reciprocal Exchange ◽  
Sequence Selection ◽  
Living Organisms ◽  
Dna Double Helix

DNA is well-known as the genetic material of living organisms. Its most prominent feature is that it contains information that enables it to replicate itself. This information is contained in the well-known Watson-Crick base pairing interactions, adenine with thymine and guanine with cytosine. The double helical structure that results from this complementarity has become a cultural icon of our era. To produce species more diverse than the DNA double helix, we use the notion of reciprocal exchange, which leads to branched molecules. The topologies of these species are readily programmed through sequence selection; in many cases, it is also possible to program their structures. Branched species can be connected to one another using the same interactions that genetic engineers use to produce their constructs, cohesion by molecules tailed in complementary single-stranded overhangs, known as ‘sticky ends.’ Such sticky-ended cohesion is used to produce N-connected objects and lattices [1]. This notion is shown in the drawing, which shows cohesion between sticky-ended branched species.

DNA Topoisomerases of Leishmania Parasites; Druggable Targets for Drug Discovery

2019 ◽  
Vol 26 (32) ◽  
pp. 5900-5923 ◽  
Author(s):  
Rosa M. Reguera ◽  
Ehab K. Elmahallawy ◽  
Carlos García-Estrada ◽  
Rubén Carbajo-Andrés ◽  
Rafael Balaña-Fouce
Keyword(s):  
Low Income ◽  
Therapeutic Potential ◽  
Double Helix ◽  
Low Income Countries ◽  
Public Health Importance ◽  
Dna Topoisomerases ◽  
Cellular Processes ◽  
Living Organisms ◽  
Dna Double Helix ◽  
Leishmania Parasites

DNA topoisomerases (Top) are a group of isomerase enzymes responsible for controlling the topological problems caused by DNA double helix in the cell during the processes of replication, transcription and recombination. Interestingly, these enzymes have been known since long to be key molecular machines in several cellular processes through overwinding or underwinding of DNA in all living organisms. Leishmania, a trypanosomatid parasite responsible for causing fatal diseases mostly in impoverished populations of low-income countries, has a set of six classes of Top enzymes. These are placed in the nucleus and the single mitochondrion and can be deadly targets of suitable drugs. Given the fact that there are clear differences in structure and expression between parasite and host enzymes, numerous studies have reported the therapeutic potential of Top inhibitors as antileishmanial drugs. In this regard, numerous compounds have been described as Top type IB and Top type II inhibitors in Leishmania parasites, such as camptothecin derivatives, indenoisoquinolines, indeno-1,5- naphthyridines, fluoroquinolones, anthracyclines and podophyllotoxins. The aim of this review is to highlight several facts about Top and Top inhibitors as potential antileishmanial drugs, which may represent a promising strategy for the control of this disease of public health importance.

scholarly journals Women in Science: 50 Fearless Pioneers Who Changed the World by R. Ignotofsky

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Hanne Pearce
Keyword(s):  
Digital Literacy ◽  
Particle Physics ◽  
Double Helix ◽  
Women Scientists ◽  
Women In Science ◽  
Theory Of Relativity ◽  
The World ◽  
Information Work ◽  
The Many ◽  
Dna Double Helix

Ignotofsky, Rachel. Women in Science: 50 Fearless Pioneers Who Changed the World. 10 Speed Press, 2016.“It’s a Scientific Fact: Women rock!” This is the statement on the back cover of Rachel Ignotofsky’s fabulous book about women in science. This illustrated hardcover book surveys 50 women scientists’ achievements and biographies in bold style. The book includes women scientists ranging from agriculture, mathematics, chemistry, geology all the way to particle physics and astronomy. Each scientist has been allotted a two-page spread with a full-page biography, that is illustrated with bright and colourful drawings relevant to their discoveries and areas of research. Dispersed between the biographies are info-graphic sections that showcase scientific implements, a glossary, and even statistics about women in STEM.I was immediately drawn to this book by the colourful illustrations (also drawn by Ignotofsky) on both the cover and interlaced throughout the glossy pages of this book. The biographies strike an excellent balance between detail and brevity. I thoroughly enjoyed reading about the many women scientists I had never learned about before, like Hypatia, a mathematician who lived in Alexandria, Egypt in 350 CE, Emmy Noether who worked for Einstein’s team on the theory of relativity, Cecilia Payne-Gaposchkin who discovered the sun was comprised of Hydrogen and Helium and Rosalind Franklin who discovered the DNA double helix. This book left me with an overwhelming sense of the remarkable discoveries by women in science.Women in Science can be enjoyed all ages of readers, including adults. Older readers will enjoy the facts and information within the biographies, while younger readers can read the many illustrations. This book would be especially great to share with young girls, to inspire curiosity and interest in the sciences, and to show that they can follow in the footsteps of many great women scientists. Highly recommended.Highly recommended: 4 out of 4 stars Reviewer: Hanne PearceHanne Pearce has worked at the University of Alberta Libraries since 2004. She holds a BA and MLIS and is currently working towards her Master of Arts in Communications and Technology. Her research interests include: visual communication, digital literacy, information literacy and the intersections between communication work and information work. She is also a freelance photographer and graphic designer.

Computational determination of radiation damage effects on DNA structure

Open Physics ◽  
2003 ◽  
Vol 1 (1) ◽  
Author(s):  
Miroslav Pinak
Keyword(s):  
Structural Changes ◽  
Double Helix ◽  
Helical Structure ◽  
Electrostatic Energy ◽  
Necessary Condition ◽  
Enzyme Complex ◽  
Repair Enzyme ◽  
Thymine Dimer ◽  
Thymine Glycol ◽  
Double Helical Structure

AbstractMolecular dynamics (MD) studies of several radiation originated lesions on the DNA molecules are presented. The pyrimidine lesions (cytosinyl radical, thymine dimer, thymine glycol) and purine lesion (8-oxoguanine) were subjected to the MD simulations for several hundred picoseconds using MD simulation code AMBER 5.0 (4.0). The simulations were performed for fully dissolved solute molecules in water. Significant structural changes in the DNA double helical structure were observed in all cases which may be categorized as: a) the breaking of hydrogen bonds network between complementary bases and resulted opening of the double helix (cytosinyl, radical, 8-oxoguanine); b) the sharp bending of the DNA helix centered at the lesion site (thymine dimer, thymine glycol); and c) the flippingout of adenine on the strand complementary to the lesion (8-oxoguanine). These changes related to the overall collapsing of the double helical structure around the lesion, are expected to facilitate the docking of the repair enzyme into the DNA in the formation of DNA-enzyme complex. The stable DNA-enzyme complex is a necessary condition for the onset of the enzymatic repair process. In addition to structural changes, specific values of electrostatic interaction energy were determined at several lesion sites (thymine dimer, thymine glycol and 8-oxoguanine). This lesion-specific electrostatic energy is a factor that enables repair enzyme to discriminate lesion from the native site during the scanning of the DNA surface.

Protamine-DNA interaction

1978 ◽  
Vol 36 (2) ◽  
pp. 200-201
Author(s):  
D.P. Bazett-Jones ◽  
F.P. Ottensmeyer
Keyword(s):  
Small Volume ◽  
Double Helix ◽  
Dna Interaction ◽  
Dark Field ◽  
Sperm Head ◽  
Nuclear Proteins ◽  
Field Electron Microscopy ◽  
Dark Field Electron ◽  
Dna Double Helix ◽  
Positively Charged

Dark field electron microscopy has been used for the study of the structure of individual macromolecules with a resolution to at least the 5Å level. The use of this technique has been extended to the investigation of structure of interacting molecules, particularly the interaction between DNA and fish protamine, a class of basic nuclear proteins of molecular weight 4,000 daltons.Protamine, which is synthesized during spermatogenesis, binds to chromatin, displaces the somatic histones and wraps up the DNA to fit into the small volume of the sperm head. It has been proposed that protamine, existing as an extended polypeptide, winds around the minor groove of the DNA double helix, with protamine's positively-charged arginines lining up with the negatively-charged phosphates of DNA. However, viewing protamine as an extended protein is inconsistent with the results obtained in our laboratory.

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