Nucleobase Protection of Deoxyribo‐
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Alternative Biochemistries for Alien Life: Basic Concepts and Requirements for the Design of a Robust Biocontainment System in Genetic Isolation
G C A T T A C G G C A T genes Review Alternative Biochemistries for Alien Life: Basic Concepts and Requirements for the Design of a Robust Biocontainment System in Genetic Isolation Christian Diwo 1 and Nediljko Budisa 1,2,* 1 Institut für Chemie, Technische Universität Berlin Müller-Breslau-Straße 10, 10623 Berlin, Germany; [email protected] 2 Department of Chemistry, University of Manitoba, 144 Dysart Rd, 360 Parker Building, Winnipeg, MB R3T 2N2, Canada * Correspondence: [email protected] or [email protected]; Tel.: +49-30-314-28821 or +1-204-474-9178 Received: 27 November 2018; Accepted: 21 December 2018; Published: 28 December 2018 Abstract: The universal genetic code, which is the foundation of cellular organization for almost all organisms, has fostered the exchange of genetic information from very different paths of evolution. The result of this communication network of potentially beneficial traits can be observed as modern biodiversity. Today, the genetic modification techniques of synthetic biology allow for the design of specialized organisms and their employment as tools, creating an artificial biodiversity based on the same universal genetic code. As there is no natural barrier towards the proliferation of genetic information which confers an advantage for a certain species, the naturally evolved genetic pool could be irreversibly altered if modified genetic information is exchanged. We argue that an alien genetic code which is incompatible with nature is likely to assure the inhibition of all mechanisms of genetic information transfer in an open environment. The two conceivable routes to synthetic life are either de novo cellular design or the successive alienation of a complex biological organism through laboratory evolution. -
Self-Catalyzed Site-Specific Depurination of Guanine Residues Within Gene Sequences
Self-catalyzed site-specific depurination of guanine residues within gene sequences Olga Amosova*, Richard Coulter, and Jacques R. Fresco* Department of Molecular Biology, Princeton University, Princeton, NJ 08544 Edited by Jack W. Szostak, Massachusetts General Hospital, Boston, MA, and approved January 19, 2006 (received for review September 28, 2005) A self-catalyzed, site-specific guanine-depurination activity has been found to occur in short gene sequences with a potential to form a stem-loop structure. The critical features of that catalytic intermediate are a 5-G-T-G-G-3 loop and an adjacent 5-T⅐A-3 base pair of a short duplex stem stable enough to fix the loop structure required for depurination of its 5-G residue. That residue is uniquely depurinated with a rate some 5 orders of magnitude faster than that of random ‘‘spontaneous’’ depurination. In con- trast, all other purine residues in the sequence depurinate at the spontaneous background rate. The reaction requires no divalent cations or other cofactors and occurs under essentially physiolog- ical conditions. Such stem-loops can form in duplex DNA under superhelical stress, and their critical sequence features have been found at numerous sites in the human genome. Self-catalyzed stem-loop-mediated depurination leading to flexible apurinic sites may therefore serve some important biological role, e.g., in nu- cleosome positioning, genetic recombination, or chromosome su- perfolding. ͉ ͉ DNA self-catalysis guanine depurination stem-loop structure Fig. 1. Localization of the cleavage site. A 32P-labeled 8-nt oligomer com- plementary to the 3Ј end of D-1 was used as a primer in a Sanger sequencing epurination in DNA has been recognized as a spontaneous reaction. -
Role of Sam68 in Dna Damage Responses and Tumorigenesis
ROLE OF SAM68 IN DNA DAMAGE RESPONSES AND TUMORIGENESIS by Xin Sun A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland Dec 2016 © 2016 Xin Sun All Rights Reserved Abstract The ability to recognize and repair DNA damage through rapid and appropriate DNA damage responses is pivotal to safeguard genomic information, which is persistently challenged by internal and environmental offenses. DNA lesion initiated poly(ADP- ribosyl)ation (PARylation), catalyzed primarily by poly(ADP-ribose) polymerase 1 (PARP1), is one of the earliest post-translational modifications to orchestrate downstream DNA damage response (DDR) signaling. However, the precise mechanisms through which PARP1 is activated and poly(ADP-ribose) (PAR) is robustly synthesized are not fully understood. Converging evidence support the emerging role of RNA- binding proteins (RBPs) in promoting DNA damage repair at different stages of DDR. We discovered Src-associated substrate during mitosis of 68 kDa (Sam68) as a novel- signaling molecule in DDR. In the absence of Sam68, DNA damage-triggered PARylation and PAR-dependent DNA repair signaling were dramatically diminished. With serial cellular and biochemical assays, we revealed that Sam68 is recruited to and significantly overlaps with PARP1 at DNA lesions and that the interaction between Sam68 and PARP1 is crucial for DNA damage-initiated and PARP1-conferred PARylation. Utilizing cell lines and knockout mice, we demonstrated that Sam68- deleted cells and animals are hypersensitive to genotoxicity caused by DNA-damaging agents. In addition, loss of Sam68 delays basal cell carcinoma (BCC) onset and progression in a mouse model for basal cell carcinoma (BCC) of the skin, suggesting Sam68 is required for BCC tumorigenesis, likely through promoting tumor cell survival. -
DNA REPLICATION, REPAIR, and RECOMBINATION Figure 5–1 Different Proteins Evolve at Very Different Rates
5 THE MAINTENANCE OF DNA DNA REPLICATION, SEQUENCES DNA REPLICATION MECHANISMS REPAIR, AND THE INITIATION AND COMPLETION OF DNA REPLICATION IN RECOMBINATION CHROMOSOMES DNA REPAIR GENERAL RECOMBINATION SITE-SPECIFIC RECOMBINATION The ability of cells to maintain a high degree of order in a chaotic universe depends upon the accurate duplication of vast quantities of genetic information carried in chemical form as DNA. This process, called DNA replication, must occur before a cell can produce two genetically identical daughter cells. Main- taining order also requires the continued surveillance and repair of this genetic information because DNA inside cells is repeatedly damaged by chemicals and radiation from the environment, as well as by thermal accidents and reactive molecules. In this chapter we describe the protein machines that replicate and repair the cell’s DNA. These machines catalyze some of the most rapid and accu- rate processes that take place within cells, and their mechanisms clearly demon- strate the elegance and efficiency of cellular chemistry. While the short-term survival of a cell can depend on preventing changes in its DNA, the long-term survival of a species requires that DNA sequences be changeable over many generations. Despite the great efforts that cells make to protect their DNA, occasional changes in DNA sequences do occur. Over time, these changes provide the genetic variation upon which selection pressures act during the evolution of organisms. We begin this chapter with a brief discussion of the changes that occur in DNA as it is passed down from generation to generation. Next, we discuss the cellular mechanisms—DNA replication and DNA repair—that are responsible for keeping these changes to a minimum. -
Geochemical Influences on Nonenzymatic Oligomerization Of
bioRxiv preprint doi: https://doi.org/10.1101/872234; this version posted December 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Geochemical influences on nonenzymatic oligomerization of prebiotically relevant cyclic nucleotides Authors: Shikha Dagar‡, Susovan Sarkar‡, Sudha Rajamani‡* ‡ Department of Biology, Indian Institute of Science Education and Research, Pune 411008, India Correspondence: [email protected]; Tel.: +91-20-2590-8061 Running title: Cyclic nucleotides and emergence of an RNA World Key words: Dehydration-rehydration cycles, lipid-assisted oligomerization, cyclic nucleotides, analogue environments Dagar, S. 1 bioRxiv preprint doi: https://doi.org/10.1101/872234; this version posted December 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract The spontaneous emergence of RNA on the early Earth continues to remain an enigma in the field of origins of life. Few studies have looked at the nonenzymatic oligomerization of cyclic nucleotides under neutral to alkaline conditions, in fully dehydrated state. Herein, we systematically investigated the oligomerization of cyclic nucleotides under prebiotically relevant conditions, where starting reactants were subjected to repeated dehydration-rehydration (DH- RH) regimes, like they would have been on an early Earth. DH-RH conditions, a recurring geological theme, are driven by naturally occurring processes including diurnal cycles and tidal pool activity. These conditions have been shown to facilitate uphill oligomerization reactions in terrestrial geothermal niches, which are hypothesized to be pertinent sites for the emergence of life. -
Syllabus 2020
Amrita Center For Nanosciences and Molecular Medicine Program in the Bachelor of Science (B.Sc.) Molecular Medicine 2020 Amrita Vishwa Vidyapeetham 1 2 B.Sc-Molecular Medicine Syllabus 20BIC102 Biophysics and Bioenergetics. Preamble Connecting Physics to biology is an essential factor which eventually determines quantifying primary factors in a physical process that occur at cell level. Physics serves as a nanoscopic visualization tool to dissect such processes to reveal the information to students. This course introduces applications of Physics into Biology. Unit 1 (5 lectures) Physics: general overview, Does Physics treats disease? Why Physics for Biology and Molecular Medicine? Concepts in Physics to apply in Biology, Methods in Physics to elucidate Biology. Unit 2 (10 lectures) Bioenergetics: Laws of thermodynamics. Concept of state functions, free energy change, equilibrium constant, coupled reactions, energy charge, ATP cycle, phosphorylation potential, and phosphoryl group transfers. Electron transport in membrane for oxidative phosphorylation, Chemical basis of hydrolysis of ATP and thioesters. Redox reactions, standard redox potentials and Nernst equation. Unit 3 (10lectures) Biophysics in Medicine: Applications of physical principles in biology and its significance in the development of various biophysical methods for analysing the complexity of biological system. Principles of Medical-imaging, Image analysis, Instrumentation and Working principles, Medical applications of X-ray: Imaging, Introduction to Fluoroscopy. Unit 4 (10 lectures) Nuclear medicine and Radiotherapy: Pros and cons, Nano-bioelectronics: Monitoring and recording bioelectric signals, Transducers in physiology, Diagnostic and Therapeutic Techniques: Cardiac pace makers, Blood flow monitors, Pulmonary function analyzers, Hemodialysis machines, Defibrillators, Short/ wave diathermy, Electrically stimulated pain management, Laser: operating principles, types, Biomedical applications in surgery. -
Role of Depurination in Mutagenesis by Chemical Carcinogens1
[CANCER RESEARCH 42, 3480-3485, September 1982] 0008-5472/82/0042-0000$02.00 Role of Depurination in Mutagenesis by Chemical Carcinogens1 Roeland M. Schaaper,2 Barry W. Glickman, and Lawrence A. Loeb3 The Joseph Gottstein Memoria/ Cancer Research Laboratory, Department of Pathology, School of Medicine, University of Washington, Seattle, Washington 98195 {R. M. S., L. A. L.], and Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 [B. W.G.] ABSTRACT significant extent during the presumably modified mode of replication in SOS-induced bacteria. In these experiments, The effect of modifying <f>x"174viral DMA by the chemical apurinic sites were introduced by a combined acid-heat treat carcinogens /?-propiolactone, A/-acetoxyacetylaminofluorene ment. Although a role for other heat-acid-induced lesions can and anf/-benzo[a]pyrene diol-epoxide was investigated by not be rigorously excluded, the mutagenicity of apurinic sites transfecting the modified DMA into Escherichia coli sphero- is strongly supported by the abolition of mutagenesis by alkali plasts. Modification of the DMA in vitro by each of these agents (20) and by purified apurinic endonuclease.4 Apurinic sites was mutagenic for the <(>x174amber mutants am3 and am86. could also be important for mutagenesis by chemical carcino Mutagenicity depended on the induction of the "SOS" re gens. Modification of purines at A/3 and A/7 and of pyrimidines sponse in the host spheroplasts. Heating ß-propiolactone- at O2 positions labilizes the /V-glycosylic bond, leading to treated DNA at neutral pH caused strong inactivation such that sharply increased spontaneous depurination rates (2, 11, 22). -
Nucleobases Thin Films Deposited on Nanostructured Transparent Conductive Electrodes for Optoelectronic Applications
www.nature.com/scientificreports OPEN Nucleobases thin flms deposited on nanostructured transparent conductive electrodes for optoelectronic applications C. Breazu1*, M. Socol1, N. Preda1, O. Rasoga1, A. Costas1, G. Socol2, G. Petre1,3 & A. Stanculescu1* Environmentally-friendly bio-organic materials have become the centre of recent developments in organic electronics, while a suitable interfacial modifcation is a prerequisite for future applications. In the context of researches on low cost and biodegradable resource for optoelectronics applications, the infuence of a 2D nanostructured transparent conductive electrode on the morphological, structural, optical and electrical properties of nucleobases (adenine, guanine, cytosine, thymine and uracil) thin flms obtained by thermal evaporation was analysed. The 2D array of nanostructures has been developed in a polymeric layer on glass substrate using a high throughput and low cost technique, UV-Nanoimprint Lithography. The indium tin oxide electrode was grown on both nanostructured and fat substrate and the properties of the heterostructures built on these two types of electrodes were analysed by comparison. We report that the organic-electrode interface modifcation by nano- patterning afects both the optical (transmission and emission) properties by multiple refections on the walls of nanostructures and the electrical properties by the efect on the organic/electrode contact area and charge carrier pathway through electrodes. These results encourage the potential application of the nucleobases thin flms deposited on nanostructured conductive electrode in green optoelectronic devices. Te use of natural or nature-inspired materials in organic electronics is a dynamic emerging research feld which aims to replace the synthesized materials with natural (bio) ones in organic electronics1–3. -
Nucleobase-Containing Compounds Evoke Behavioural, Olfactory, and Transcriptional Responses in Model Fishes
Correction-Nucleobase-containing compounds evoke behavioural, olfactory, and transcriptional responses in model fishes Shamchuk, A. L., Blunt, B. J., Lyons, D. D., Wang, M. Q., Gasheva, A., Lewis, C. R., Tomlin, K., Starr Hazard, E., Hardiman, G., & Tierney, K. B. (2018). Correction-Nucleobase-containing compounds evoke behavioural, olfactory, and transcriptional responses in model fishes. FACETS, 3(1). https://doi.org/10.1139/facets-2017-0101 Published in: FACETS Document Version: Publisher's PDF, also known as Version of record Queen's University Belfast - Research Portal: Link to publication record in Queen's University Belfast Research Portal Publisher rights Copyright 2018 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. 4.0), which permits unrestricted use, General rights Copyright for the publications made accessible via the Queen's University Belfast Research Portal is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The Research Portal is Queen's institutional repository that provides access to Queen's research output. Every effort has been made to ensure that content in the Research Portal does not infringe any person's rights, or applicable UK laws. If you discover content in the Research Portal that you believe breaches copyright or violates any law, please contact [email protected]. -
Development of a Universal Nucleobase and Modified
Development of a Universal Nucleobase and UNIT 1.5 Modified Nucleobases for Expanding the Genetic Code This unit presents protocols for the synthesis and characterization of nucleosides with unnatural bases in order to develop bases for the expansion of the genetic alphabet or for nonselective pairing opposite natural bases. The faithful pairing of nucleobases through complementary hydrogen-bond (H-bond) donors and acceptors forms the foundation of the genetic code. However, there is no reason to assume that the requirements for duplex stability and replication must limit the genetic alphabet to only two base pairs, or, for that matter, hydrogen-bonded base pairs. Expansion of this alphabet to contain a third base pair would allow for the encoding of additional information and would make possible a variety of in vitro experiments using nucleic acids with unnatural building blocks. Previous efforts to generate orthogonal base pairs have relied on H-bonding patterns that are not found with the canonical Watson-Crick pairs. However, in all cases, the unnatural bases were not kinetically orthogonal, and instead competitively paired with natural bases during polymerase-catalyzed DNA synthesis (Horlacher et al., 1995; Lutz et al., 1996, 1998a,b). Tautomeric isomerism, which would alter H-bond donor and acceptor patterns, likely contributes to this kinetic infidelity (Roberts et al., 1997a,b; Robinson et al., 1998; Beaussire and Pochet, 1999). An alternative strategy is centered around developing unnatural bases that form pairs based not on hydrogen bonds, but rather on interbase hydrophobic interactions. Such hydrophobic bases should not pair stably opposite natural bases due to the forced desolvation of the purines or pyrimidines. -
Depurination of Nucleosides and Induced by 2-Bromopropane At
Depurination of Nucleosides and Calf Thymus DNA by 2-BP Bull. Korean Chem. Soc. 2009, Vol. 30, No. 10 2309 Depurination of Nucleosides and C이 f Thymus DNA Induced by 2-Bromopropane at the Physiological Condition Jyoti Sherchan, Hoyoung Choi, and Eung-Seok Lee* College of Pharmacy, Yeungnam University, Kyongsan 712-749, Korea. * E-mail: [email protected] Received July 28, 2009, Accepted August 25, 2009 Depurination, the release of purine bases from nucleic acids by hydrolysis of the N-glycosidic bond, gives rise to alterations of the cell genome. Though cells have evolved mechanisms to repair these lesions, unrepaired apurinic sites have been shown to have two biological consequences: lethality and base substitution errors. 2-Bromopropane (2-BP) is used as an intermediate in the synthesis of pharmaceuticals, dyes, and other organics. In addition, 2-BP has been used as a replacement for chloroflurocarbons and 1,1,1-trichloroethane as a cleaning solvent in electronics industry. However, 2-BP was found to cause reproductive and hematopoietic disorders in local workers exposed to it. Owing to the toxicity of 2-BP, there has been a tendency to use 1-BP as an alternative cleaning solvent to 2-BP. However, 1-BP has also been reported to be neurotoxic in rats. Though N-guanine adduct of 2-BP has been reported previously, massive depurination of the nucleosides and calf thymus DNA was observed in this study.腿 incubated the nucleosides (ddG, dG, guanosine, ddA, dA and adenosine) with excess amount 2-BP at the physiological condition (pH 7.4, 37 oC), which were analyzed by HPLC and LC-MS/MS. -
Overview of the Synthesis of Nucleoside Phosphates and Polyphosphates 13.1.6
Overview of the Synthesis of Nucleoside UNIT 13.1 Phosphates and Polyphosphates Phosphorylated nucleosides play a domi- ity to the synthesis. Side reactions can occur, nant role in biochemistry. Primary metabolism, such as depurination of the nucleoside, phos- DNA replication and repair, RNA synthesis, phorylation of the nucleobase, as well as chemi- protein synthesis, signal transduction, polysac- cal alteration of nucleobase analogs. Due to charide biosynthesis, and enzyme regulation their intrinsic reactivity, the synthesis of phos- are just a handful of processes involving these phoanhydride bonds is also synthetically chal- molecules. Literally thousands of enzymes use lenging. Phosphate anhydrides are phosphory- these compounds as substrates and/or regula- lating reagents that are readily degraded under tors. The need to obtain such compounds in acidic conditions. Finally, purification of syn- both labeled and unlabeled forms, as well as a thetic nucleotides can be problematic. Ionic burgeoning need for analogs, has driven the reagents, starting materials, and mixtures of development of a myriad of chemical and en- regioisomers (2′-, 3′-, 5′-phosphates) can be zymatic synthetic approaches. As chemical en- particularly difficult to separate from the de- tities, few molecules possess the wide array of sired product. densely packed functionality present in phos- In spite of the many potential difficulties phorylated nucleosides. This poses a formida- associated with nucleoside phosphorylation ble challenge to the synthetic chemist, one that and polyphosphorylation, a certain amount of has not yet been fully overcome. This overview success has been achieved in these areas. Given will address some common methods (synthetic the wealth of phosphorylating reagents avail- and enzymatic) used to construct phosphory- able, simple phosphorylation of nucleosides at lated nucleosides.