Journal articles: 'Writhe transition in circular DNA'

1

Gebe, John A., and J. Michael Schurr. "Thermodynamics of the first transition in writhe of a small circular DNA by Monte Carlo simulation." Biopolymers 38, no. 4 (1998): 493–503. http://dx.doi.org/10.1002/(sici)1097-0282(199604)38:4<493::aid-bip5>3.0.co;2-o.

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MILLER, DAVID, and CRAIG BENHAM. "FIXED-WRITHE ISOTOPIES AND THE TOPOLOGICAL CONSERVATION LAW FOR CLOSED, CIRCULAR DNA." Journal of Knot Theory and Its Ramifications 05, no. 06 (1996): 859–66. http://dx.doi.org/10.1142/s0218216596000461.

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Li, Xiuyan, Yangtao Fan, Qingqing Gao, Hu Chen, and Yanhui Liu. "Identification of effects of YOYO-1 intercalation on the topological states of circular DNA." Modern Physics Letters B 32, no. 20 (2018): 1850231. http://dx.doi.org/10.1142/s0217984918502317.

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YOYO-1 intercalation leads to the reduction of twist rigidity, unwinding of DNA, elongation of DNA contour length and YOYO-1 concentration-dependent persistence length, until now few works identified their roles in determining the topological states of circular DNA. Based on the convolution of the writhe distribution of circular DNA obtained by using Monte Carlo simulation and the twist distribution, effects of YOYO-1 intercalation on the linking number distribution of circular DNA are predicted and identified. YOYO-1 intercalation leads to larger fluctuation, but not to the obvious enlargement of the writhe distribution, so that the variance of the linking number distribution mainly depends on the variance of the twist distribution. The unwinding angle contributes to the drifting of the linking number distribution away from the original equilibrium value of zero and has no effects on the variance of the linking number distribution, converse to the roles of the reduced twist rigidity in the linking number distribution. Furthermore, the method used in the work can be generalized to detect the effects of other intercalators on the topological states of circular DNA.

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Tobias, Irwin. "The Twist, Writhe, and Linking Number Distributions in Closed Circular DNA." Journal of Biomolecular Structure and Dynamics 3, no. 2 (1985): 315–25. http://dx.doi.org/10.1080/07391102.1985.10508419.

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Bauer, William R., Hisako Ohtsubo, Eiichi Ohtsubo, and Craig J. Benham. "Energetics of Coupled Twist and Writhe Changes in Closed Circular pSM1 DNA." Journal of Molecular Biology 253, no. 3 (1995): 438–52. http://dx.doi.org/10.1006/jmbi.1995.0565.

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Zhang, Wenke, Stephanie Allen, Clive J. Roberts, and Panos Soultanas. "The Bacillus subtilis Primosomal Protein DnaD Untwists Supercoiled DNA." Journal of Bacteriology 188, no. 15 (2006): 5487–93. http://dx.doi.org/10.1128/jb.00339-06.

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ABSTRACT The essential Bacillus subtilis DnaD and DnaB proteins have been implicated in the initiation of DNA replication. Recently, DNA remodeling activities associated with both proteins were discovered that could provide a link between global or local nucleoid remodeling and initiation of replication. DnaD forms scaffolds and opens up supercoiled plasmids without nicking to form open circular complexes, while DnaB acts as a lateral compaction protein. Here we show that DnaD-mediated opening of supercoiled plasmids is accompanied by significant untwisting of DNA. The net result is the conversion of writhe (Wr) into negative twist (Tw), thus maintaining the linking number (Lk) constant. These changes in supercoiling will reduce the considerable energy required to open up closed circular plectonemic DNA and may be significant in the priming of DNA replication. By comparison, DnaB does not affect significantly the supercoiling of plasmids. Binding of the DnaD C-terminal domain (Cd) to DNA is not sufficient to convert Wr into negative Tw, implying that the formation of scaffolds is essential for duplex untwisting. Overall, our data suggest that the topological effects of the two proteins on supercoiled DNA are different; DnaD opens up, untwists and converts plectonemic DNA to a more paranemic form, whereas DnaB does not affect supercoiling significantly and condenses DNA only via its lateral compaction activity. The significance of these findings in the initiation of DNA replication is discussed.

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Morozov, Vladimir F., Eugene Sh Mamasakhlisov, Arsen V. Grigoryan, Artem V. Badasyan, Shura Hayryan, and Chin-Kun Hu. "Helix–coil transition in closed circular DNA." Physica A: Statistical Mechanics and its Applications 348 (March 2005): 327–38. http://dx.doi.org/10.1016/j.physa.2004.09.037.

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Sato, Y., T. Hamada, K. Kubo, T. Kishida, Mazda, and K. Yoshikawa. "2P122 Conformational Transition of DNA : Difference between Linier DNA and Circular DNA." Seibutsu Butsuri 44, supplement (2004): S140. http://dx.doi.org/10.2142/biophys.44.s140_2.

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Wu, Chenyi, and Andrew Travers. "Modelling and DNA topology of compact 2-start and 1-start chromatin fibres." Nucleic Acids Research 47, no. 18 (2019): 9902–24. http://dx.doi.org/10.1093/nar/gkz495.

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Abstract We have investigated the structure of the most compact 30-nm chromatin fibres by modelling those with 2-start or 1-start crossed-linker organisations. Using an iterative procedure we obtained possible structural solutions for fibres of the highest possible compaction permitted by physical constraints, including the helical repeat of linker DNA. We find that this procedure predicts a quantized nucleosome repeat length (NRL) and that only fibres with longer NRLs (≥197 bp) can more likely adopt the 1-start organisation. The transition from 2-start to 1-start fibres is consistent with reported differing binding modes of the linker histone. We also calculate that in 1-start fibres the DNA constrains more torsion (as writhe) than 2-start fibres with the same NRL and that the maximum constraint obtained is in accord with previous experimental results. We posit that the coiling of the fibre is driven by overtwisting of linker DNA which, in the most compact forms - for example, in echinoderm sperm and avian erythrocytes - could adopt a helical repeat of ∼10 bp/turn. We argue that in vivo the total twist of linker DNA could be modulated by interaction with other abundant chromatin-associated proteins and by epigenetic modifications of the C-terminal tail of linker histones.

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Tomanee, Panarat, and James T. Hsu. "Transition Between Supercoiled and Open Circular Plasmid DNA During Alcohol Precipitation." Journal of Liquid Chromatography & Related Technologies 27, no. 10 (2004): 1483–90. http://dx.doi.org/10.1081/jlc-120034086.

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Bednar, Jan, Patrick Furrer, Andrzej Stasiak, Jacques Dubochet, Edward H. Egelman, and Andrew D. Bates. "The Twist, Writhe and Overall Shape of Supercoiled DNA Change During Counterion-induced Transition from a Loosely to a Tightly Interwound Superhelix." Journal of Molecular Biology 235, no. 3 (1994): 825–47. http://dx.doi.org/10.1006/jmbi.1994.1042.

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12

Hu, Pei-Jia, Tie-Feng Fang, Ai-Min Guo, and Qing-Feng Sun. "Aharonov–Bohm-like effects and Fano resonances in circular DNA molecular junctions." Applied Physics Letters 121, no. 15 (2022): 154102. http://dx.doi.org/10.1063/5.0118229.

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DNA electronics has reattracted great interest in recent years and showed a number of fascinating phenomena. Here, we present a theoretical study of electron transport through a two-terminal circular DNA junction under a perpendicular magnetic field. Our results indicate that this circular DNA exhibits Aharonov–Bohm-like effects and a semiconductor–insulator–semiconductor transition by tuning this magnetic field, with the transmission spectrum nearly oscillating periodically. Interestingly, Fano resonances appear around integer multiples of the magnetic flux quantum accompanied by several vortices of local currents. Moreover, the circular DNA behaves as a nanoscale switch, and this switching effect is robust and could be improved for longer molecular length and weaker molecule–electrode coupling, with the on/off ratio exceeding 104 for long circular DNA. These results may help for designing novel circular DNA-based molecular devices.

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Majumdar, Rabi, Ansuman Lahiri, and Srikanta Sen. "Theory of a supercoil-induced B-Z transition in closed circular DNA." Journal of Molecular Structure: THEOCHEM 230 (May 1991): 431–35. http://dx.doi.org/10.1016/0166-1280(91)85194-c.

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14

Wang, Lijiang, and Timothy A. Keiderling. "Vibrational circular dichroism studies of the A-to-B conformational transition in DNA." Biochemistry 31, no. 42 (1992): 10265–71. http://dx.doi.org/10.1021/bi00157a013.

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Strychalski, Elizabeth A., Samuel M. Stavis, and Jon Geist. "A localized transition in the size variation of circular DNA in nanofluidic slitlike confinement." AIP Advances 3, no. 4 (2013): 042115. http://dx.doi.org/10.1063/1.4802594.

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Choi, Vivian W., Douglas M. McCarty, and R. Jude Samulski. "Host Cell DNA Repair Pathways in Adeno-Associated Viral Genome Processing." Journal of Virology 80, no. 21 (2006): 10346–56. http://dx.doi.org/10.1128/jvi.00841-06.

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ABSTRACT Recentstudies have shown that wild-type and recombinant adeno-associated virus (AAV and rAAV) genomes persist in human tissue predominantly as double-stranded (ds) circular episomes derived from input linear single-stranded virion DNA. Using self-complementary recombinant AAV (scAAV) vectors, we generated intermediates that directly transition to ds circular episomes. The scAAV genome ends are palindromic hairpin-structured terminal repeats, resembling a double-stranded break repair intermediate. Utilizing this substrate, we found cellular DNA recombination and repair factors to be essential for generating circular episomal products. To identify the specific cellular proteins involved, the scAAV circularization-dependent vector was used as a reporter in 19 mammalian DNA repair-deficient cell lines. The results show that RecQ helicase family members (BLM and WRN), Mre11 and NBS1 of the Mre11-Rad50-Nbs1 (MRN) complex, and ATM are required for efficient scAAV genome circularization. We further demonstrated that the scAAV genome requires ATM and DNA-PKCS, but not NBS1, to efficiently convert to a circular form in nondividing cells in vivo using transgenic mice. These studies identify specific pathways involved for further elucidating viral and cellular mechanisms of DNA maintenance important to the viral life cycle and vector utilizations.

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Benková, Zuzana, and Peter Cifra. "Comparison of linear and ring DNA macromolecules moderately and strongly confined in nanochannels." Biochemical Society Transactions 41, no. 2 (2013): 625–29. http://dx.doi.org/10.1042/bst20120279.

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Understanding the mechanism of DNA extension in nanochannels is necessary for interpretation of experiments in nanofluidic channel devices that have been conducted recently with both linear and ring chains. The present article reviews the situation with linear chains and analyses the experimental results and simulations for channel-induced extension (linearization) of ring chains. Results for confined rings indicate a transition between moderate and strong confinement similar to that of linear chains. Owing to stronger self-avoidance in confined rings, the transition and chain extension is shifted relative to linear DNA. We suggest that a relationship similar to that used for the extension of linear chains may also be used for circular DNA.

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Miller, F. D., J. B. Rattner, and J. H. van de Sande. "Assembly of DNA onto the histone octamer facilitates the B-to-Z transition." Bioscience Reports 6, no. 5 (1986): 467–76. http://dx.doi.org/10.1007/bf01116138.

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Nucleosomal core particles containing the right- and left-handed conformations of DNA were examined for their ability to support the B→Z or Z→B transition. Nucleosomes were assembled onto the B- and Z-conformations of poly[d(Gm5C)] and the B-conformation of poly[d(GC)] as previously described (1). Absorbance and circular dichroic spectroscopy indicated that the DNA on all three core particle populations could undergo the conformational B↔Z transition. Further, the right- to left-handed transition for both poly[d(Gm5C)] and poly[d(GC)] appeared to be facilitated by the DNAs association with the histone octamer. The DNA remained associated with the protein core subsequent to the transition, and electron microscopy and sedimentation velocity analysis indicated that there were no gross changes in nucleosomal structure. However, a change in the sedimentation value of the poly[d(Gm5C)] core particles was detected when the conformation of the DNA was altered from B to Z, resulting in a lower S20,w value for the Z-form particles than for the corresponding B-form particles.

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19

Lewis, Frederick D. "DNA photonics." Pure and Applied Chemistry 78, no. 12 (2006): 2287–95. http://dx.doi.org/10.1351/pac200678122287.

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Short DNA duplexes can be stabilized by the presence of organic chromophores, which serve as hairpin linkers or end-capping groups. Capped hairpins possessing one or more base pairs form stable folded structures in aqueous solution. Increasing the number of base pairs separating the two chromophores increases both the distance between the two chromophores and the dihedral angle between their electronic transition dipoles. Thus, duplex DNA can serve as a helical scaffold for the study of electronic interactions between two chromophores. Three types of electronic interaction have been investigated: (a) exciton coupling (EC) between two identical chromophores, as probed by exciton-coupled circular dichroism (EC-CD); (b) fluorescence resonance energy transfer (FRET) between a fluorescent donor and acceptor; and (c) photoinduced electron transfer (PET) between an electron donor and acceptor. EC and the efficiency of fluorescence energy transfer are dependent upon both the distance and dihedral angle separating the two chromophores. Electron transfer occurs via both single-step superexchange and bridge-mediated hopping mechanisms, neither of which displays angular dependence. The competition between these mechanisms is dependent upon both the energetics of hole injection into the base-pair bridge and the distance between the donor and acceptor chromophores, superexchange dominating at short distance and hole hopping at longer distances.

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Blasiak, Janusz, Vladimír Kleinwächter, Zofia Walter, and Renata Žaludová. "Interaction of Organophosphorus Insecticide Methylparathion with Calf Thymus DNA and a Synthetic DNA Duplex." Zeitschrift für Naturforschung C 50, no. 11-12 (1995): 820–23. http://dx.doi.org/10.1515/znc-1995-11-1213.

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Abstract The interaction of an organophosphorus insecticide methylparathion (O.O-dimethyl 0-4-nitrophenyl phosphorothioate) with double-stranded DNA was characterized by UV and circular dichroism (CD) spectroscopy. Two kinds of DNA were employed: calf thymus DNA (CT DNA) and a synthetic two-stranded oligomer of sequence 5′-d(TTGGATCCGAATT-CAAGCTT)-3′ Melting curves and CD spectra were taken for the DNAs in the presence of the insecticide at methylparathion/DNA base pair molar ratio of 0.5. The insecticide evoked a decrease of the melting temperature and a broadening of the transition range for CT DNA. Similar effects were observed for the synthetic oligomer but they were less pronounced than in the case of CT DNA. Methylparathion evoked a slight shift and an increase in the amplitude of the negative band in the CD spectra of both DNAs. Obtained results indicate that methylparathion may perturb the thermal stability and conformation of DNA, which is an evidence that the insecticide has an ability to interact directly with DNA.

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Wang, Bao-Zhong, Xu-Bin Wei, and Wang-Yi Liu. "Cleavage of Supercoiled Circular Double-stranded DNA Induced by a Eukaryotic Cambialistic Superoxide Dismutase from Cinnamomum camphora." Acta Biochimica et Biophysica Sinica 36, no. 9 (2004): 609–17. http://dx.doi.org/10.1093/abbs/36.9.609.

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Abstract A eukaryotic cambialistic superoxide dismutase (SOD) has been purified to homogeneity from mature seeds of the disease- and insect-resistant camphor tree (Cinnamomum camphora). Besides the known role of this SOD in protecting cells against oxidative stress, it can induce the cleavage of supercoiled double-stranded DNA into nicked and linear DNA. It can not cleave linear DNA or RNA, demonstrating there is no DNase or RNase in the purified cambialistic SOD. Furthermore, the SOD can linearize circular pGEM-4Z DNA that is relaxed by topoisomerase I. This result indicates that the DNA-cleaving activity requires substrates being topologically constrained. The supercoiled DNA-cleaving activity of the cambialistic SOD can be inhibited by either SOD inhibitor (azide) or catalase and hydroxyl radical scavengers (ethanol and mannitol). The chelator of iron, diethylenetriaminepentaacetic acid (DTPA), also inhibits the supercoiled DNA-cleaving activity. These results show that the dismutation activity is crucial for the supercoiled DNA cleavage. The modification of tryptophan residue of the cambialistic SOD with N-bromosuccinimide (NBS) shows that these two activities are structurally correlative. The reaction mechanism is proposed that the hydroxyl radical formed in a transition-metal-catalyzing Fenton-type reaction contributes to the DNA-cleaving activity. In addition, the cleavage sites in supercoiled pGEM-4Z DNA are random.

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Andrushchenko, Valery, Helmut Wieser, and Petr Bouř. "B−Z Conformational Transition of DNA Monitored by Vibrational Circular Dichroism. Ab Initio Interpretation of the Experiment." Journal of Physical Chemistry B 106, no. 48 (2002): 12623–34. http://dx.doi.org/10.1021/jp0262721.

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Grigoryan, A. V., A. V. Badasyan, E. Sh Mamasakhlisov, and V. F. Morozov. "The invariance of order parameter and temperature redefinition in helix-coil transition theory of circular closed DNA." Physics of Atomic Nuclei 68, no. 10 (2005): 1685–88. http://dx.doi.org/10.1134/1.2121917.

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Babu, M. S. Surendra, T. B. Patrudu та K. Hussain Reddy. "DNA Binding and Cleavage Activity of Binuclear Metal Complexes with Benzil-α-Monoxime Thiosemicarbzone". E-Journal of Chemistry 8, s1 (2011): S309—S317. http://dx.doi.org/10.1155/2011/567979.

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Transition metal complexes of copper(II), nickel(II), cobalt(II) and iron(II) with benzil-α-monoxime thiosemicarbazone (BMOT) have been synthesized and characterized by molar conductance, magnetic moments, IR, electronic and ESR spectroscopy. Electrochemical behaviors of these complexes were investigated by cyclic voltammetric studies. The nuclease activity of these complexes has been investigated on double-stranded pBR322 circular plasmid DNA by using the gel electrophoresis experiments in presence and absence of oxidant (H2O2). In the absence of oxidant DNA cleavage by hydrolytically was observed a less discernable, whereas in presence of oxidant (H2O2) all complexes showed increased nuclease activity.

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Ermakov, E., L. Smirnova, L. Sinyanskii, et al. "Anti-DNA antibodies in the blood of patients with schizophrenia possess DNA-hydrolyzing activity." European Psychiatry 33, S1 (2016): s247—s248. http://dx.doi.org/10.1016/j.eurpsy.2016.01.628.

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IntroductionAutoantibodies (Abs) to different neuronal receptors and DNA were detected in the blood of patients with schizophrenia. Abs hydrolyzing DNA were detected in pool of polyclonal autoantibodies in autoimmune and infectious diseases, such catalytic Abs were named abzymes.ObjectivesTo investigate the level of anti-DNA antibodies and DNA-hydrolyzing activity of IgG from the serum of patients with schizophrenia depending on leading clinical symptoms.Aims– To measure the concentration of anti-DNA Abs in serum of patients with leading positive and negative symptoms;– to determine DNA-hydrolyzing activity of IgG.MethodsIn our study, 51 patients were included. The levels of antiDNA Abs were determined using ELISA. DNA-hydrolyzing activity was detected as the level(%) of supercoiled pBluescript DNA transition in circular and linear forms. Statistical analysis was performed in “Statistica 9.0”.ResultsAnti-DNA Abs of patients with schizophrenia not only bind DNA, but quite efficiently hydrolyze the substrate. IgG of patient with schizophrenia were shown to possess DNA hydrolyzing activity. It should be noted that DNAase activity of IgG in patients with schizophrenia with a negative symptoms was significantly higher, than in patients with positive symptoms (Table 1).ConclusionsThe data show a correlation with the level of DNase activity and leading symptoms of patients with schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Lee, Jeremy S., Laura J. P. Latimer, and R. Stephen Reid. "A cooperative conformational change in duplex DNA induced by Zn2+ and other divalent metal ions." Biochemistry and Cell Biology 71, no. 3-4 (1993): 162–68. http://dx.doi.org/10.1139/o93-026.

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Zn2+ and some other divalent metal ions bind to duplex DNA at pHs above 8 and cause a conformational change. This new structure does not bind ethidium, allowing the development of a rapid fluorescence assay. All duplex DNAs, regardless of sequence or G∙C content, can form this structure. The rate of formation shows a strong dependence on temperature, pH, and Zn2+ concentration; at 20 °C, 1 mM Zn2+, and pH 8.6 the dismutation is half complete in 30 min. Addition of EDTA causes rapid reversion to 'B' DNA, showing that the new conformation retains two strands that are antiparallel. Unlike the ultraviolet or circular dichroism spectra, the nuclear magnetic resonance spectrum was informative since the imino protons of both A∙T and G∙C base pairs are lost upon addition of a stoichiometric amount of Zn2+. The pitch of the helix was estimated from gel electrophoresis of circular DNAs in the presence of Zn2+ and it contains at least 5% fewer base pairs per turn than 'B' DNA. The transformation is cooperative and shows hysteresis, suggesting that this is a distinct structure and not simply a minor variant of 'B' DNA. It is proposed to call this new structure 'M' DNA because of the intimate involvement of metal ions.Key words: DNA conformation, cooperative transition, ethidium binding, divalent metal ions, proton nuclear magnetic resonance.

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Bhavsar, Yogini P., Samantha M. Reilly, and Randy M. Wadkins. "Evaluation of Fluorescent Analogs of Deoxycytidine for Monitoring DNA Transitions from Duplex to Functional Structures." Journal of Nucleic Acids 2011 (2011): 1–7. http://dx.doi.org/10.4061/2011/986820.

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Topological variants of single-strand DNA (ssDNA) structures, referred to as “functional DNA,” have been detected in regulatory regions of many genes and are thought to affect gene expression. Two fluorescent analogs of deoxycytidine, Pyrrolo-dC (PdC) and 1,3-diaza-2-oxophenoxazine (t), can be incorporated into DNA. Here, we describe spectroscopic studies of both analogs to determine fluorescent properties that report on structural transitions from double-strand DNA (dsDNA) to ssDNA, a common pathway in the transition to functional DNA structures. We obtained fluorescence-detected circular dichroism (FDCD) spectra, steady-state fluorescence spectra, and fluorescence lifetimes of the fluorophores in DNA. Our results show that PdC is advantageous in fluorescence lifetime studies because of a distinct ~2 ns change between paired and unpaired bases. However, t is a better probe for FDCD experiments that report on the helical structure of DNA surrounding the fluorophore. Both fluorophores provide complementary data to measure DNA structural transitions.

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Yevdokimov, Yuri, Sergey Skuridin, Viktor Salyanov, Sergey Semenov, and Efim Kats. "Liquid-Crystalline Dispersions of Double-Stranded DNA." Crystals 9, no. 3 (2019): 162. http://dx.doi.org/10.3390/cryst9030162.

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In this review, we compare the circular dichroism (CD) spectra of liquid-crystalline dispersion (LCD) particles formed in PEG-containing aqueous-salt solutions with the purpose of determining the packing of ds DNA molecules in these particles. Depending on the osmotic pressure of the solution, the phase exclusion of ds DNA molecules at room temperature results in the formation of LCD particles with the cholesteric or the hexagonal packing of molecules. The heating of dispersion particles with the hexagonal packing of the ds DNA molecules results in a new phase transition, accompanied by an appearance of a new optically active phase of ds DNA molecules. Our results are rationalized by way of a concept of orientationally ordered “quasinematic” layers formed by ds DNA molecules, with a parallel alignment in the hexagonal structure. These layers can adopt a twisted configuration with a temperature increase; and as a result of this process, a new, helicoidal structure of dispersion particle is formed (termed as the “re-entrant” cholesteric phase). To prove the cholesteric pattern of ds DNA molecules in this phase, the “liquid-like” state of the dispersion particles was transformed into its “rigid” counterpart.

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Ng, K. H., J. Maigne, and J. Deschatrette. "The inductive effect of a human DNA sequence (HALF1) on the differentiation of a variant rat hepatoma cell (C2) is restricted to episomal forms of the molecule." Journal of Cell Science 108, no. 4 (1995): 1703–13. http://dx.doi.org/10.1242/jcs.108.4.1703.

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HALF1, a 4.3 kb human DNA sequence, was originally identified as a double-stranded, closed-circular DNA molecule in revertants from a dedifferentiated rat hepatoma cell (C2) transfected with human liver DNA. Here we report its specific properties in inducing the transition to the hepatic phenotype. (i) In vitro recircularized HALF1 induces reversion after a minimum time lag of 7 days post-transfection. (ii) After induction, the presence of HALF1 is not required for maintaining the induced hepatic state. (iii) HALF1 is detected as a sequence integrated in high molecular mass DNA of human liver. (iv) HALF1 monomer or dimer plasmid constructs do not induce reversion when integrated into the genome of transfectants. (v) Short ubiquitous RNA transcripts (approximately 400 bases) are detected with specific HALF1 probes. These results indicate that the reversion process is linked to the presence of HALF1 extrachromosomal molecules.

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Müller, Sabrina, Jannik Paulus, Jochen Mattay, Heiko Ihmels, Veronica I. Dodero, and Norbert Sewald. "Photocontrolled DNA minor groove interactions of imidazole/pyrrole polyamides." Beilstein Journal of Organic Chemistry 16 (January 9, 2020): 60–70. http://dx.doi.org/10.3762/bjoc.16.8.

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Azobenzenes are photoswitchable molecules capable of generating significant structural changes upon E-to-Z photoisomerization in peptides or small molecules, thereby controlling geometry and functionality. E-to-Z photoisomerization usually is achieved upon irradiation at 350 nm (π–π* transition), while the Z-to-E isomerization proceeds photochemically upon irradiation at >400 nm (n–π* transition) or thermally. Photoswitchable compounds have frequently been employed as modules, e.g., to control protein–DNA interactions. However, their use in conjunction with minor groove-binding imidazole/pyrrole (Im/Py) polyamides is yet unprecedented. Dervan-type Im/Py polyamides were equipped with an azobenzene unit, i.e., 3-(3-(aminomethyl)phenyl)azophenylacetic acid, as the linker between two Im/Py polyamide strands. Only the (Z)-azobenzene-containing polyamides bound to the minor groove of double-stranded DNA hairpins. Photoisomerization was exemplarily evaluated by 1H NMR experiments, while minor groove binding of the (Z)-azobenzene derivatives was proven by CD titration experiments. The resulting induced circular dichroism (ICD) bands of the bound ligands, together with the photometric determination of the dsDNA melting temperature, revealed a significant stabilization of the DNA upon association with the ligand. The (Z)-azobenzene acted as a building block inducing a reverse turn, which favored hydrogen bonds between the pyrrole/imidazole amide and the DNA bases. In contrast, the E-configured polyamides did not induce any ICD characteristic for minor groove binding. The incorporation of the photoswitchable azobenzene unit is a promising strategy to obtain photoswitchable Im/Py hairpin polyamides capable of interacting with the dsDNA minor groove only in the Z-configuration.

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Lambowitz, Alan M., and Chia-Chien Chiang. "The Mauriceville and Varkud plasmids: primitive retroelements found in Neurospora mitochondria." Canadian Journal of Botany 73, S1 (1995): 173–79. http://dx.doi.org/10.1139/b95-242.

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The Mauriceville and closely related Varkud plasmids are small circular DNAs (3.6 and 3.7 kb, respectively) found in the mitochondria of certain Neurospora spp. strains isolated from nature. The plasmids replicate via reverse transcription and appear to be primitive retroelements that may be related to the early ancestors of retroviruses. Recent studies have shown that the plasmid reverse transcriptase closely resembles certain viral RNA-dependent RNA polymerases in initiating (−) strand cDNA synthesis de novo (i.e., without a primer) at a tRNA-like structure at the 3′ end of the plasmid transcript. The plasmid reverse transcriptase can also use DNA or RNA primers and can carry out template-switching reactions that lead to the generation of suppressive mutant plasmids or the integration of the plasmids into mitochondrial DNA. The characteristics of the plasmids and their reverse transcription mechanism suggest an evolutionary connection between RNA and DNA replication and raise the possibility that the plasmids are related to the earliest DNA-based life forms that emerged at the time of transition from an RNA to a DNA world. Key words: DNA synthesis, evolution, retrovirus, reverse transcriptase, RNA virus.

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Hafenstein, Susan, та Bentley A. Fane. "φX174 Genome-Capsid Interactions Influence the Biophysical Properties of the Virion: Evidence for a Scaffolding-Like Function for the Genome during the Final Stages of Morphogenesis". Journal of Virology 76, № 11 (2002): 5350–56. http://dx.doi.org/10.1128/jvi.76.11.5350-5356.2002.

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ABSTRACT During the final stages of φX174 morphogenesis, there is an 8.5-Å radial collapse of coat proteins around the packaged genome, which is tethered to the capsid's inner surface by the DNA-binding protein. Two approaches were taken to determine whether protein-DNA interactions affect the properties of the mature virion and thus the final stages of morphogenesis. In the first approach, genome-capsid associations were altered with mutant DNA-binding proteins. The resulting particles differed from the wild-type virion in density, native gel migration, and host cell recognition. Differences in native gel migration were especially pronounced. However, no differences in protein stoichiometries were detected. An extragenic second-site suppressor of the mutant DNA-binding protein restores all assayed properties to near wild-type values. In the second approach, φX174 was packaged with foreign, single-stranded, covalently closed, circular DNA molecules identical in length to the φX174 genome. The resulting particles exhibited native gel migration rates that significantly differed from the wild type. The results of these experiments suggest that the structure of the genome and/or its association with the capsid's inner surface may perform a scaffolding-like function during the procapsid-to- virion transition.

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Haga, Nobuyuki, Toshinori Usui, Yasuhiro Takenaka, Yuta Chiba, and Tomoaki Abe. "Immaturin-Nuclease as a Model System for a Gene-Programmed Sexual Development and Rejuvenescence in Paramecium Life History." Microorganisms 11, no. 1 (2022): 82. http://dx.doi.org/10.3390/microorganisms11010082.

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Fertilization-initiated development and adult-onset aging are standard features in the life history of eukaryotes. In Paramecium, the number of cell divisions after the birth of a new generation is an essential parameter of sexual phase transition and aging. However, the gene driving this process and its evolutionary origin have not yet been elucidated. Here we report several critical outcomes obtained by molecular genetics, immunofluorescence microscopy, transformation by microinjection, and enzymological analysis. The cloned immaturin gene induces sexual rejuvenation in both mature and senescent cells by microinjection. The immaturin gene originated from proteobacteria’s glutathione-S-transferase (GST) gene. However, immaturin has been shown to lose GST activity and instead acquire nuclease activity. In vitro substrates for immaturin-nuclease are single- and double-stranded DNA, linear and circular DNA, and single-stranded viral genome RNA such as coronavirus. Anti-immaturin antibodies have shown that the subcellular localizations of immaturin are the macronucleus, cytoplasm, cell surface area, and cilia. The phase transition of sexuality is related to a decrease in the intracellular abundance of immaturin. We propose that sexual maturation and rejuvenation is a process programmed by the immaturin gene, and the sexual function of each age is defined by both the abundance and the intracellular localization mode of the immaturin-nuclease.

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Frandi, Antonio, and Justine Collier. "Multilayered control of chromosome replication in Caulobacter crescentus." Biochemical Society Transactions 47, no. 1 (2019): 187–96. http://dx.doi.org/10.1042/bst20180460.

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Abstract The environmental Alphaproteobacterium Caulobacter crescentus is a classical model to study the regulation of the bacterial cell cycle. It divides asymmetrically, giving a stalked cell that immediately enters S phase and a swarmer cell that stays in the G1 phase until it differentiates into a stalked cell. Its genome consists in a single circular chromosome whose replication is tightly regulated so that it happens only in stalked cells and only once per cell cycle. Imbalances in chromosomal copy numbers are the most often highly deleterious, if not lethal. This review highlights recent discoveries on pathways that control chromosome replication when Caulobacter is exposed to optimal or less optimal growth conditions. Most of these pathways target two proteins that bind directly onto the chromosomal origin: the highly conserved DnaA initiator of DNA replication and the CtrA response regulator that is found in most Alphaproteobacteria. The concerted inactivation and proteolysis of CtrA during the swarmer-to-stalked cell transition license cells to enter S phase, while a replisome-associated Regulated Inactivation and proteolysis of DnaA (RIDA) process ensures that initiation starts only once per cell cycle. When Caulobacter is stressed, it turns on control systems that delay the G1-to-S phase transition or the elongation of DNA replication, most probably increasing its fitness and adaptation capacities.

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Mukerji, Ishita, and Alison P. Williams. "UV Resonance Raman and Circular Dichroism Studies of a DNA Duplex Containing an A3T3Tract: Evidence for a Premelting Transition and Three-Centered H-Bonds†." Biochemistry 41, no. 1 (2002): 69–77. http://dx.doi.org/10.1021/bi010918i.

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Schulte, U., and A. M. Lambowitz. "The LaBelle mitochondrial plasmid of Neurospora intermedia encodes a novel DNA polymerase that may be derived from a reverse transcriptase." Molecular and Cellular Biology 11, no. 3 (1991): 1696–706. http://dx.doi.org/10.1128/mcb.11.3.1696-1706.1991.

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The LaBelle-1b strain of Neurospora intermedia contains a 4.1-kb closed-circular mitochondrial plasmid DNA, which encodes a single long open reading frame of 1,151 amino acids reported to have sequence similarity to reverse transcriptases. Here, we show that the LaBelle strain contains a novel DNA polymerase activity that is highly specific for the endogenous LaBelle plasmid DNA in nucleoprotein particles and can be distinguished from the mitochondrial DNA polymerase by several characteristics. Photolabeling experiments indicate that the LaBelle-specific DNA polymerase activity is associated with a polypeptide of 120 kDa, which is in good agreement with the size predicted for the protein encoded by the LaBelle plasmid open reading frame (132 kDa). This 120-kDa polypeptide is found only in the LaBelle strain that contains the mitochondrial plasmid, and it cosegregates with mitochondria in sexual crosses, suggesting that it is encoded by the plasmid. The LaBelle-specific DNA polymerase efficiently uses the artificial DNA substrates, poly(dA)-oligo(dT) and poly(dC)-oligo(dG), but despite its reported sequence similarity to reverse transcriptases, it has very low activity with analogous RNA substrates, poly(rA)-oligo(dT), poly(rC)-oligo(dG), or poly(rCm)-oligo(dG). Considered together with the previous sequence comparisons, our results suggest that the LaBelle plasmid encodes a novel DNA polymerase, which was derived from a protein that was at one time a reverse transcriptase but lost its ability to use RNA templates. This DNA polymerase now presumably functions in replication of the plasmid. Our results constitute the first biochemical evidence for a DNA polymerase activity associated with a mitochondrial plasmid. Further, they may provide insight into the evolution of DNA polymerases from reverse transcriptases, as presumably occurred in the course of evolution following the transition from the so-called RNA world to the present DNA world.

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37

Schulte, U., and A. M. Lambowitz. "The LaBelle mitochondrial plasmid of Neurospora intermedia encodes a novel DNA polymerase that may be derived from a reverse transcriptase." Molecular and Cellular Biology 11, no. 3 (1991): 1696–706. http://dx.doi.org/10.1128/mcb.11.3.1696.

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The LaBelle-1b strain of Neurospora intermedia contains a 4.1-kb closed-circular mitochondrial plasmid DNA, which encodes a single long open reading frame of 1,151 amino acids reported to have sequence similarity to reverse transcriptases. Here, we show that the LaBelle strain contains a novel DNA polymerase activity that is highly specific for the endogenous LaBelle plasmid DNA in nucleoprotein particles and can be distinguished from the mitochondrial DNA polymerase by several characteristics. Photolabeling experiments indicate that the LaBelle-specific DNA polymerase activity is associated with a polypeptide of 120 kDa, which is in good agreement with the size predicted for the protein encoded by the LaBelle plasmid open reading frame (132 kDa). This 120-kDa polypeptide is found only in the LaBelle strain that contains the mitochondrial plasmid, and it cosegregates with mitochondria in sexual crosses, suggesting that it is encoded by the plasmid. The LaBelle-specific DNA polymerase efficiently uses the artificial DNA substrates, poly(dA)-oligo(dT) and poly(dC)-oligo(dG), but despite its reported sequence similarity to reverse transcriptases, it has very low activity with analogous RNA substrates, poly(rA)-oligo(dT), poly(rC)-oligo(dG), or poly(rCm)-oligo(dG). Considered together with the previous sequence comparisons, our results suggest that the LaBelle plasmid encodes a novel DNA polymerase, which was derived from a protein that was at one time a reverse transcriptase but lost its ability to use RNA templates. This DNA polymerase now presumably functions in replication of the plasmid. Our results constitute the first biochemical evidence for a DNA polymerase activity associated with a mitochondrial plasmid. Further, they may provide insight into the evolution of DNA polymerases from reverse transcriptases, as presumably occurred in the course of evolution following the transition from the so-called RNA world to the present DNA world.

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Li, Jiahe, Rongping Liu, Jinzhang Jiang, et al. "Zinc(II) Terpyridine Complexes: Substituent Effect on Photoluminescence, Antiproliferative Activity, and DNA Interaction." Molecules 24, no. 24 (2019): 4519. http://dx.doi.org/10.3390/molecules24244519.

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A series of ZnCl2 complexes (compounds 1–10) with 4′-(substituted-phenyl)-2,2′:6′,2′′-terpyridine that bears hydrogen (L1), p-methyl (L2), p-methoxy (L3), p-phenyl (L4), p-tolyl (L5), p-hydroxyl (L6), m-hydroxyl (L7), o-hydroxyl (L8), p-carboxyl (L9), or p-methylsulfonyl (L10) were prepared and then characterized by 1H NMR, electrospray mass-spectra (ESI-MS), IR, elemental analysis, and single crystal X-ray diffraction. In vitro cytotoxicity assay was used to monitor the antiproliferative activities against tumor cells. Absorption spectroscopy, fluorescence titration, circular dichroism spectroscopy, and molecular modeling studied the DNA interactions. All of the compounds display interesting photoluminescent properties and different maximal emission peaks due to the difference of the substituent groups. The cell viability studies indicate that the compounds have excellent antiproliferative activity against four human carcinoma cell lines, A549, Bel-7402, MCF-7, and Eca-109, with the lowest IC50 values of 0.33 (10), 0.66 (6), 0.37 (7), and 1.05 (7) μM, respectively. The spectrophotometric results reveal that the compounds have strong affinity binding with DNA as intercalator and induce DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π…π stacking and hydrogen bonds, providing an order of nucleotide sequence binding selectivity as ATGC > ATAT > GCGC. These compounds intercalate into the base pairs of the DNA of the tumor cells to affect their replication and transcription, and the process is supposed to play an important role in the anticancer mechanism.

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D’Ercole, Jacopo, Sean W. J. Prosser, and Paul D. N. Hebert. "A SMRT approach for targeted amplicon sequencing of museum specimens (Lepidoptera)—patterns of nucleotide misincorporation." PeerJ 9 (January 14, 2021): e10420. http://dx.doi.org/10.7717/peerj.10420.

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Natural history collections are a valuable resource for molecular taxonomic studies and for examining patterns of evolutionary diversification, particularly in the case of rare or extinct species. However, the recovery of sequence information is often complicated by DNA degradation. This article describes use of the Sequel platform (Pacific Biosciences) to recover the 658 bp barcode region of the mitochondrial cytochrome c oxidase I (COI) gene from 380 butterflies with an average age of 50 years. Nested multiplex PCR was employed for library preparation to facilitate sequence recovery from extracts with low concentrations of highly degraded DNA. By employing circular consensus sequencing (CCS) of short amplicons (circa 150 bp), full-length barcodes could be assembled without a reference sequence, an important advance from earlier protocols which required reference sequences to guide contig assembly. The Sequel protocol recovered COI sequences (499 bp on average) from 318 of 380 specimens (84%), much higher than for Sanger sequencing (26%). Because each read derives from a single molecule, it was also possible to quantify the incidence of substitutions arising from DNA damage. In agreement with past work on sequence changes induced by DNA degradation, the transition C/G → T/A was the most prevalent category of change, but its rate of occurrence (4.58E−4) was so low that it did not impede the recovery of reliable sequences. Because the current protocol recovers COI sequence from most museum specimens, and because sequence fidelity is unaffected by nucleotide misincorporations, large-scale sequence characterization of museum specimens is feasible.

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40

Vijayanathan, Veena, Norma J. Greenfield, T. J. Thomas та ін. "Effects of estradiol and 4-hydroxytamoxifen on the conformation, thermal stability, and DNA recognition of estrogen receptor β". Biochemistry and Cell Biology 85, № 1 (2007): 1–10. http://dx.doi.org/10.1139/o06-144.

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Estrogen receptors (ERα and ERβ) are ligand-activated transcription factors. We examined the effects of estradiol (E2), 4-hydroxytamoxifen (HT), and the estrogen response element (ERE) on the helical content and thermal unfolding of ERβ. A circular dichroism (CD) spectrum of ERβ showed changes at 210 and 222 nm that were due to the presence of E2, which is indicative of partial unfolding. In contrast, HT did not alter the CD spectrum of ERβ. The addition of E2 + ERE caused an increase in the α-helical content and an increase in the temperature midpoint of folding transition (TM) from 39 ± 0.7 °C to 57.2 ± 1 °C. The addition of E2 + mutant ERE, or E2 + control oligonucleotide, increased the TM of ERβ to 45 ± 2 °C only. In the presence of HT, ERβ yielded similar TM values (55–58 °C) with ERE, mutant ERE, or control oligodeoxynucleotide. The binding affinity of ERβ for ERE increased 125.7-fold as a result of the presence of E2, but only 4-fold as a result of HT. These results demonstrate coupled effects of E2 and ERE on ERβ stability and binding affinity. The increased thermal stability of HT–ERβ–ERE was associated with reduced specificity of ERβ–ERE recognition, illustrating profound differences in conformational states of ERβ induced by E2 and HT.

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41

Katsafanas, George C., and Bernard Moss. "Vaccinia Virus Intermediate Stage Transcription Is Complemented by Ras-GTPase-activating Protein SH3 Domain-binding Protein (G3BP) and Cytoplasmic Activation/Proliferation-associated Protein (p137) Individually or as a Heterodimer." Journal of Biological Chemistry 279, no. 50 (2004): 52210–17. http://dx.doi.org/10.1074/jbc.m411033200.

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Transcription of the DNA genome of vaccinia virus occurs in the cytoplasm and is temporally programmed by early, intermediate, and late stage-specific transcription factors in conjunction with a viral multisubunit RNA polymerase. The RNA polymerase, capping enzyme, and three factors (VITF-1, VITF-2, and VITF-3) are sufficient forin vitrotranscription of a DNA template containing an intermediate stage promoter. Vaccinia virus intermediate transcription factor (VITF)-1 and -3 are virus-encoded, whereas VITF-2 was partially purified from extracts of uninfected HeLa cells. Using purified and recombinant viral proteins, we showed that the HeLa cell factor was required for transcription of linear or nicked circular templates but not of super coiled DNA. HeLa cell polypeptides of ∼110 and 66 kDa copurified with VITF-2 activity through multiple chromatographic steps. The polypeptides were separated by SDS-polyacrylamide gel electrophoresis and identified by mass spectrometry as Ras-GTPase-activating protein SH3 domain-binding protein (G3BP) and p137, recently named cytoplasmic activation/proliferation-associated protein-1. The co-purification of the two polypeptides with transcription-complementing activity was confirmed with specific antibodies, and their association with each other was demonstrated by affinity chromatography of tagged recombinant forms. Furthermore, recombinant G3BP and p137 expressed individually or together in mammalian or bacterial cells complemented the activity of the viral RNA polymerase and transcription factors. The involvement of cellular proteins in transcription of intermediate stage genes may regulate the transition between early and late phases of vaccinia virus replication.

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42

Li, Jiahe, Min Chen, Jinzhang Jiang, et al. "A New Concept of Enhancing the Anticancer Activity of Manganese Terpyridine Complex by Oxygen-Containing Substituent Modification." International Journal of Molecular Sciences 24, no. 4 (2023): 3903. http://dx.doi.org/10.3390/ijms24043903.

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Eleven manganese 4′-substituted-2,2′:6′,2″-terpyridine complexes (1a–1c and 2a–2h) with three non-oxygen-containing substituents (L1a–L1c: phenyl, naphthalen-2-yl and naphthalen-1-yl, L1a–L1c) and eight oxygen-containing substituents (L2a–L2h: 4-hydroxyl-phenyl, 3-hydroxyl-phenyl, 2-hydroxyl-phenyl, 4-methoxyl-phenyl, 4-carboxyl-phenyl, 4-(methylsulfonyl)phenyl, 4-nitrophenyl and furan-2-yl) were prepared and characterized by IR, elemental analysis or single crystal X-ray diffraction. In vitro data demonstrate that all of these show higher antiproliferative activities than cisplatin against five human carcinoma cell lines: A549, Bel-7402, Eca-109, HeLa and MCF-7. Compound 2d presents the strongest antiproliferative effect against A549 and HeLa cells, with IC50 values being 0.281 μM and 0.356 μM, respectively. The lowest IC50 values against Bel-7402 (0.523 μM) Eca-109 (0.514 μM) and MCF-7 (0.356 μM) were obtained for compounds 2h, 2g and 2c, respectively. Compound 2g with a nitro group showed the best results on the whole, with relevantly low IC50 values against all the tested tumor cells. The DNA interactions with these compounds were studied by circular dichroism spectroscopic and molecular modeling methods. Spectrophotometric results revealed that the compounds have strong affinities in binding with DNA as intercalators, and the binding induces DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π–π stacking and hydrogen bonds. The anticancer activities of the compounds are correlated with their DNA binding ability, and the modification of oxygen-containing substituents significantly enhanced the anticancer activity, which could provide a new rationale for the future design of terpyridine-based metal complexes with antitumor potential.

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Masternak, Joanna, Agnieszka Gilewska, Barbara Barszcz, et al. "Ruthenium(II) and Iridium(III) Complexes as Tested Materials for New Anticancer Agents." Materials 13, no. 16 (2020): 3491. http://dx.doi.org/10.3390/ma13163491.

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The oncological use of cisplatin is hindered by its severe side effects and a very important resistance problem. To overcome these problems, scientists have attempted to design new generation transition-metal anticancer complexes. In this study, we present new complexes, ruthenium(II) [(η6-p-cymene)RuCl(py2CO)]PF6 (1), iridium(III) [(η5-Cp)IrCl(py2CO)]PF6 (2), and NH4[IrCl4(py2CO)]·H2O (3), based on di-2-pyridylketone (py2CO). The prepared complexes were characterized by FTIR, 1H, 13C, 15N NMR, UV-Vis, PL and elemental analysis techniques. The single-crystal X-ray structure analysis and comparative data revealed pseudo-octahedral half-sandwich 1 and 2 complexes and octahedral tetrachloroiridate(III) 3 with a rare chelating κ2N,O coordination mode of py2CO. The compounds were tested in vitro against three cancer cell lines—colorectal adenoma (LoVo), myelomonocytic leukaemia (MV-4-11), breast adenocarcinoma (MCF-7), and normal fibroblasts (BALB/3T3). The most promising results were obtained for iridium(III) complex 3 against MV-4-11 (IC50 = 35.8 ± 13.9 µg/mL) without a toxic effect against normal BALB/3T3, which pointed towards its selectivity as a potential anticancer agent. Extensive research into their mode of binding with DNA confirmed for 1 and 2 complexes non-classical binding modes, while the 3D circular dichroism (CD) experiment (ΔTm) suggested that 3 induced the probable formation of covalent bonds with DNA. In addition, the obtained iridium complexes induce ROS, which, in synergy with hydrolysis promoting DNA bonding, may lead to cancer cell death.

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Liu, Zhiwen, Ying Wang, Shaoqun Shu, Juan Cai, Chengyuan Tang, and Zheng Dong. "Non-coding RNAs in kidney injury and repair." American Journal of Physiology-Cell Physiology 317, no. 2 (2019): C177—C188. http://dx.doi.org/10.1152/ajpcell.00048.2019.

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Acute kidney injury (AKI) is a major kidney disease featured by a rapid decline of renal function. Pathologically, AKI is characterized by tubular epithelial cell injury and death. Besides its acute consequence, AKI contributes critically to the development and progression of chronic kidney disease (CKD). After AKI, surviving tubular cells regenerate to repair. Normal repair restores tubular integrity, while maladaptive or incomplete repair results in renal fibrosis and eventually CKD. Non-coding RNAs (ncRNAs) are functional RNA molecules that are transcribed from DNA but not translated into proteins, which mainly include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), small nucleolar RNAs (snoRNAs), and tRNAs. Accumulating evidence suggests that ncRNAs play important roles in kidney injury and repair. In this review, we summarize the recent advances in the understanding of the roles of ncRNAs, especially miRNAs and lncRNAs in kidney injury and repair, discuss the potential application of ncRNAs as biomarkers of AKI as well as therapeutic targets for treating AKI and impeding AKI-CKD transition, and highlight the future research directions of ncRNAs in kidney injury and repair.

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Malarvizhi, M., G. Subramanian, and PR Athappan. "Template Synthesis, Spectral and Redox Behavior of Metal Complexes of Macrocyclic Tetraaza Schiff Base and their Interaction with Herring Sperm DNA." Materials Science Forum 699 (September 2011): 205–29. http://dx.doi.org/10.4028/www.scientific.net/msf.699.205.

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This paper documents the detailed investigation of the relationship between molecular structure and biological activity of few tetraaza macrocyclic metal (II) complexes equipped by the template condensation of o-bromoaniline, ethylenediamine and salbenz in 2:1:1 ratio with metal (II) salts (1mM). All these complexes are found to be stable in air and soluble in CN3CN or DMSO, and are characterized through spectral (UV-Vis, IR, EPR) and electrochemical methods. A square planar geometry is proposed for Cu(II), Ni(II) and Co(II) complexes, while an octahedral geometry is suggested for Mn(II) and Fe(II). The IR spectra indicate that the NH groups of the amine exist as such even after complexation without deprotonation, and all the complexes show a strong band in 1580-1590 cm-1region corresponding to ν(C=N), due to coordinated azomethine group to the metal. The solution electronic spectra of these complexes show intense LMCT bands around 400 nm. Intense electronic absorption spectra as well as the four line pattern in EPR spectra with broad g⊥suggests that the copper(II) complexes have distorted square planar geometry. On titration with herring sperm DNA, CuN4,CoN4,NiN4and MnN4complexes exhibit an abrupt amend in their electronic spectrum and cyclic voltammogram. The intense intraligand π-π* transition in the region 350–420 nm is found to show hypochromicity on titration with DNA in all these complexes, due to their electrostatic interaction with DNA. All these complexes show one well–defined quasi-reversible redox couple with values ranging from ∆Ep 137 to 337 mV. Their spectral and electrochemical outcome designate that the square planar complexes Cu(II), Co(II) and Ni(II) interact much better than the axially coordinated octahedral complexes Mn(II) and Fe(II). The decrease found in the negative absorption peak, characteristic peak due to helicity of DNA, in circular dichroism studies reflects the perversion in the helical nature of B-DNA upon the addition of complex. The binding of plasmid DNA by these complexes has also been investigated by agarose gel electrophoresis, remarkably Ni(II) complex was found to cleave the DNA double helix.

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46

Kuo, Dennis J., Norman J. Lacayo, Don Hoang, et al. "Array CGH Discovers Novel Genomic Signatures in De Novo Acute Myeloid Leukemia (AML): Results of Children’s Oncology Group (COG) Study POG #9421." Blood 106, no. 11 (2005): 2771. http://dx.doi.org/10.1182/blood.v106.11.2771.2771.

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Abstract Acute myeloid leukemia (AML) is a heterogeneous disease. Risk factors such as karyotype, FAB subtype, FLT3 status and response to induction therapy are determinants of outcome with current therapies. We hypothesize that array comparative genomic hybridization (CGH) will identify gene copy number changes that are determinants of outcome. Array CGH was performed on diagnostic bone marrow samples from patients on the COG study POG #9421. In order to determine regions of altered gene copy number, labeled genomic DNA samples were hybridized together with sex-matching normal human reference DNA to cDNA microarrays with 41,751 features (corresponding to 24,473 unique Unigene cluster IDs), arrays were obtained from the Stanford University Microarray Core Facility. Control hybridizations were performed to assess intra- and inter-experimental variability. We studied 70 samples with adequate high-quality DNA. Circular binary segmentation was used to distinguish discrete gene copy number transition points from chance noise events and to transform primary clone-by-clone data into genomic regions of equal copy number. Using gain/loss threshold, based on two-standard deviation range of control self-to-self distribution, novel gene amplifications and deletions were found in profiled samples. The highest alteration recurrence was observed for gains of chromosome 8 (21%) and losses of chromosome 6 (29%). The area of chromosome 8 which was found to be gained is notable for the presence of potential oncogenes such as ERK8. The deleted area of chromosome 6 is notable for the presence of potential regulators of oncogenesis: MDC1, DDR1, NFKBIL1, TNF, and BRD2. In summary, array CGH has identified novel areas of gene copy number gain and loss in this population of pediatric de novo AML patients. Further studies are needed to assess whether these genes are associated with outcome, known risk factors and whether they will provide insight into the heterogeneity of de novo AML.

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Bayly, Richard, Takayuki Murase, Brandy D. Hyndman, et al. "Critical Role for a Single Leucine Residue in Leukemia Induction by E2A-PBX1." Molecular and Cellular Biology 26, no. 17 (2006): 6442–52. http://dx.doi.org/10.1128/mcb.02025-05.

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ABSTRACT In roughly 5% of cases of acute lymphoblastic leukemia, a chromosomal translocation leads to expression of the oncogenic protein E2A-PBX1. The N-terminal portion of E2A-PBX1, encoded by the E2A gene, is identical in sequence to the corresponding portion of the E proteins E12/E47 and includes transcriptional activation domains. The C terminus consists of most of the HOX interacting transcription factor PBX1, including its DNA-binding homeodomain. Structure-function correlative experiments have suggested that oncogenesis by E2A-PBX1 requires an activation domain, called AD1, at the extreme N terminus. We recently demonstrated that a potentially helical portion of AD1 interacts directly with the transcriptional coactivator protein cyclic AMP response element-binding protein (CBP) and that this interaction is essential in the immortalization of primary bone marrow cells in tissue culture. Here we show that a conserved LXXLL motif within AD1 is required in the interaction between E2A-PBX1 and the KIX domain of CBP. We show by circular dichroism spectroscopy that the LXXLL-containing portion of AD1 undergoes a helical transition upon interacting with the KIX domain and that amino acid substitutions that prevent helix formation prevent both the KIX interaction and cell immortalization by E2A-PBX1. Perhaps most strikingly, substitution of a single, conserved leucine residue (L20) within the LXXLL motif impairs leukemia induction in mice after transplantation with E2A-PBX1-expressing bone marrow. The KIX domain of CBP mediates well-characterized interactions with several transcription factors of relevance to leukemia induction. Circumstantial evidence suggests that the side chain of L20 might interact with a deep hydrophobic pocket in the KIX domain. Therefore, our results serve to identify a potential new drug target.

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Kumar, Challa V., Inoka K. Deshapriya, Michael R. Duff, Brett Blakeley, and Denise Lee Haye. "Novel, Simple, Versatile and General Synthesis of Nanoparticles Made from Proteins, Nucleic Acids and other Materials." Journal of Nano Research 12 (December 2010): 77–88. http://dx.doi.org/10.4028/www.scientific.net/jnanor.12.77.

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A new, simple, and versatile method was developed to prepare protein nanoparticles, for the first time, and the approach was extended to prepare organic, inorganic, and biological nanomaterials. For example, nanoparticles of met-hemoglobin and glucose oxidase are readily prepared by contacting a fine spray of aqueous solutions of the proteins to an organic solvent such as methanol or acetonitrile. The protein nanoparticles suspended in organic solvents retained their secondary structure and biological activities to a significant extent. Using this approach, we also successfully prepared nanoparticles of transition metal complexes, organic molecules, nucleic acids, inorganic polymers, and organic polymers. Particle size depended on reagent concentrations, pH and the solvent used, and particle sizes have been controlled from 20 to 200 nm by adjusting these parameters. In each case, particle sizes and size distributions were determined by dynamic light scattering and the data have been confirmed by electron microscopy. Addition of appropriate electrolytes to the nanoparticle supensions stabilized them against aggregation or crystallization, and particles were stable over months of storage at 4°C. Nanoparticles of met-hemoglobin, glucose oxidase, and calf thymus DNA indicated retention of their native-like structures, as evidenced from their respective circular dichroism spectra. Enzyme nanoparticles retained their catalytic activities to a significant extent. For example, peroxidase-like activity of met-hemoglobin nanoparticles suspended in methanol was 0.3 M-1 s-1, which is comparable to the activity of met-hmoglobin in aqueous buffer (1.0 M-1 s-1) even though the former has been measured in methanol. This activity is far greater than the activity of free heme in methanol. Thus, the nanobiocatalysts retained substantial activity in organic solvents. Nanoparticles of anthracene indicated extensive excitonic coupling due to inter-chromophore interactions. The current method of nanoparticle synthesis is rapid, simple, versatile, reproducible and resulted in the formation of nanoparticles from a variety of materials, many of them for the first time.

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Bar, Amir, Alkan Kabakçıoğlu, and David Mukamel. "Constrained thermal denaturation of DNA under fixed linking number." Open Physics 10, no. 3 (2012). http://dx.doi.org/10.2478/s11534-012-0070-7.

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AbstractA DNA molecule with freely fluctuating ends undergoes a sharp thermal denaturation transition upon heating. However, in circular DNA chains and some experimental setups that manipulate single DNA molecules, the total number of turns (linking number) is constant at all times. The consequences of this additional topological invariant on the melting behaviour are nontrivial. Below, we investigate the melting characteristics of a homogeneous DNA where the linking number along the melting curve is preserved by supercoil formation in duplex portions. We obtain the mass fraction and the number of loops and supercoils below and above the melting temperature. We also argue that a macroscopic loop appears at T c and calculate its size as a function of temperature.

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Smrek, Jan, Iurii Chubak, Christos N. Likos, and Kurt Kremer. "Active topological glass." Nature Communications 11, no. 1 (2020). http://dx.doi.org/10.1038/s41467-019-13696-z.

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AbstractThe glass transition in soft matter systems is generally triggered by an increase in packing fraction or a decrease in temperature. It has been conjectured that the internal topology of the constituent particles, such as polymers, can cause glassiness too. However, the conjecture relies on immobilizing a fraction of the particles and is therefore difficult to fulfill experimentally. Here we show that in dense solutions of circular polymers containing (active) segments of increased mobility, the interplay of the activity and the topology of the polymers generates an unprecedented glassy state of matter. The active isotropic driving enhances mutual ring threading to the extent that the rings can relax only in a cooperative way, which dramatically increases relaxation times. Moreover, the observed phenomena feature similarities with the conformation and dynamics of the DNA fibre in living nuclei of higher eukaryotes.

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Journal articles on the topic 'Writhe transition in circular DNA'

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