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We report the high‐resolution NMR solution‐state structure of an intramolecular G‐quadruplex with a diagonal loop of ten nucleotides. The G‐quadruplex is formed by a 34‐nt DNA sequence, d[CAG3T2A2G3TATA2CT3AG4T2AG3T2], named UpsB‐Q‐1. This sequence is found within promoters of the var genes of Plasmodium falciparum, which play a key role in malaria pathogenesis and evasion of the immune system. The [3+1]‐hybrid G‐quadruplex formed under physiologically relevant conditions exhibits a unique equilibrium between two structures, both stabilized by base stacking and non‐canonical hydrogen bonding. Unique equilibrium of the two closely related 3D structures originates from a North‐South repuckering of deoxyribose moiety of residue T27 in the lateral loop. Besides the 12 guanines involved in three G‐quartets, most residues in loop regions are involved in interactions at both G‐quartet‐loop interfaces. [ABSTRACT FROM AUTHOR]

Although more than 10% of the human genome has the potential to fold into non- B DNA, the formation of non-canonical structural motifs as part of long dsDNA chains are usually considered as unfavorable from a thermodynamic point of view. However, recent experiments have confirmed that non-canonical motifs do exist and are non-randomly distributed in genomic DNA. This distribution is highly dependent not only on the DNA sequence but also on various other factors such as environmental conditions, DNA topology and the expression of specific cellular factors in different cell types. In this study, we describe a new strategy used in the preparation of DNA minicircles containing different non-canonical motifs which arise as a result of imperfect base pairing between complementary strands. The approach exploits the fact that imperfections in the pairing of complementary strands thermodynamically weaken the dsDNA structure at the expense of enhancing the formation of non-canonical motifs. In this study, a completely different concept of stable integration of a non-canonical motif into dsDNA is presented. Our approach allows the integration of various types of non-canonical motifs into the dsDNA structure such as hairpin, cruciform, G-quadruplex and i-motif forms but also combinations of these forms. Small DNA minicircles have recently become the subject of considerable interest in both fundamental research and in terms of their potential therapeutic applications. [ABSTRACT FROM AUTHOR]

DNA, a significant physiological biometric, is present in all human cells like hair, blood, and skin. This research introduces a new approach called the Deep DNA Learning Network (DDLN) for person identification based on their DNA. This novel Machine Learning model is designed to gather DNA chromosomes from an individual's parents. The model's flexibility allows it to expand or contract and has the capability to determine one or both parents of an individual using the provided chromosomes. Notably, the DDLN model offers quick training in comparison to traditional deep learning methods. The study employs two real datasets from Iraq: the Real Iraqi Dataset for Kurds (RIDK) and the Real Iraqi Dataset for Arabs (RIDA). The outcomes demonstrate that the proposed DDLN model achieves an Equal Error Rate (EER) of 0 for both datasets, indicating highly accurate performance. [ABSTRACT FROM AUTHOR]

5‐Azacytosine (5‐AC) is one of the best interesting noncanonical nucleobases due to its functionalization and structural imitation of natural bases. 5‐AC can be used as the scaffold of two important chemotherapeutic medicines, 5‐azacytidine and 2′‐deoxy‐5‐azacytidine. Furthermore, increased sensitivity to UV leads to the photochemical effects of 5‐AC also attracted attention. Yet, no study has been reported to explore the effect of glycosyl groups on the photophysical and photochemical properties of 5‐AC, which can help to reveal the photostability of related actual clinic drugs. In this study, the excited‐state dynamics of 5‐azacytidine and 2′‐deoxy‐5‐azacytidine are studied by femtosecond transient absorption and quantum‐chemical calculations while revisiting that of 5‐AC with a wider probe spectral range. It is shown that glycosyl substitution on the N1 position leads to ultrafast excited‐state relaxation within several picoseconds in both nucleosides, which is distinct compared with the 17 ps lifetime seen in 5‐AC. It is proposed that these changes are due to altering the energy level of the dark nπ* state. Moreover, our results suggest that it should be cautioned to simply replace sugar groups with methyl groups when doing a theoretical calculation study on nucleobases and their derivatives. [ABSTRACT FROM AUTHOR]

To improve the chemical regulation on the activity of cyclic dinucleotides (CDNs), we here designed a reduction-responsive dithioethanol (DTE)-based dCDN prodrug 9 (DTE-dCDN). Prodrug 9 improved the cell permeability with the intracellular levels peaking in 2 h in THP-1 cells. Under the reductive substance such as GSH or DTT, prodrug 9 could be quickly decomposed in 30 min to release the parent dCDN. In THP1-Lucia cells, prodrug 9 also retained a high bioactivity with the EC50 of 0.96 μM, which was 51-, 43-, and 3-fold more than the 2′,3′-cGAMP (EC50 = 48.6 μM), the parent compound 3′,3′-c-di-dAMP (EC50 = 41.3 μM), and ADU-S100 (EC50 = 2.9 μM). The high bioactivity of prodrug 9 was validated to be highly correlated with the activation of the STING signaling pathway. Furthermore, prodrug 9 could also improve the transcriptional expression levels of IFN-β, CXCL10, IL-6, and TNF-α in THP-1 cells. These results will be helpful to the development of chemically controllable CDN prodrugs with a high cellular permeability and potency. [ABSTRACT FROM AUTHOR]

Aims: The existence of modified ribonucleotide monophosphates embedded in genomic DNA, as a consequence of oxidative stress conditions, including 8-oxo-guanosine and ribose monophosphate abasic site (rAP), has been recently highlighted by several works and associated with oxidative stress conditions. Although human apurinic-apyrimidinic endodeoxyribonuclease 1 (APE1), a key enzyme of the base-excision repair pathway, repairs rAP sites and canonical deoxyribose monophosphate abasic sites with similar efficiency, its incision-repairing activity on 8-oxo-guanosine is very weak. The aims of this work were to: (i) identify proteins able to specifically bind 8-oxo-guanosine embedded in DNA and promote APE1 endoribonuclease activity on this lesion, and (ii) characterize the molecular and biological relevance of this interaction using human cancer cell lines. Results: By using an unbiased proteomic approach, we discovered that the AU-rich element RNA-binding protein 1 (AUF1) actively recognizes 8-oxo-guanosine and stimulates the APE1 enzymatic activity on this DNA lesion. By using orthogonal approaches, we found that: (i) the interaction between AUF1 and APE1 is modulated by H2O2-treatment; (ii) depletion of APE1 and AUF1 causes the accumulation of single- and double- strand breaks; and (iii) both proteins are involved in modulating the formation of DNA:RNA hybrids. Innovation: These results establish unexpected functions of AUF1 in modulating genome stability and improve our knowledge of APE1 biology with respect to 8-oxo-guanosine embedded in DNA. Conclusion: By showing a novel function of AUF1, our findings shed new light on the process of genome stability in mammalian cells toward oxidative stress-related damages. Antioxid. Redox Signal. 39, 411–431. [ABSTRACT FROM AUTHOR]

Photographic investigations of rising bubbles in seawater revealed that each bubble may conduct a single or bi-spiraling motion, which resemble architecture of RNA or DNA respectively. The rotational motion results from acceleration of ionic hydrates, which are separated to anionic and cationic domains at the upper and bottom curvatures of the bubble. Afterwards, rotational motion undergoes further acceleration in the bubble upper vortex, followed by deceleration at the vortex tip. During that phase, the spiraling motion cause significant friction that result in polarization of electronegative atoms of H, C, N, O and P. These may be simultaneously arranged around a whirling cationic strands and form phosphate groups, ribose and nitrogen bases equipped with H2 and H3 rotors. It is hypothesized that such hydrogen rotors may operate as generators of electrons, which may be detached from valence shells of electropositive atoms. Then, electrons may flow via nitrogen bases and deoxyribose or ribose to phosphate groups. Next, the negatively charged edges of phosphate groups may attract cationic hydrates and energize their rotational motion in the grooves, then causing also its spiraling projection outward. That may be responsible for replication of nucleotides and its arrangement along the cationic flow into RNA or DNA polymers, in the same manner as originally produced by rising bubbles. Moreover, it points that hydrogen rotors may generate energy needed for viability as well as interact with all physical and chemical fields. [ABSTRACT FROM AUTHOR]

When modified uridine derivatives are incorporated into DNA, radical species may form that cause DNA damage. This category of molecules has been proposed as radiosensitizers and is currently being researched. Here, we study electron attachment to 5-bromo-4-thiouracil (BrSU), a uracil derivative, and 5-bromo-4-thio-2′-deoxyuridine (BrSdU), with an attached deoxyribose moiety via the N-glycosidic (N1-C) bond. Quadrupole mass spectrometry was used to detect the anionic products of dissociative electron attachment (DEA), and the experimental results were supported by quantum chemical calculations performed at the M062X/aug-cc-pVTZ level of theory. Experimentally, we found that BrSU predominantly captures low-energy electrons with kinetic energies near 0 eV, though the abundance of bromine anions was rather low compared to a similar experiment with bromouracil. We suggest that, for this reaction channel, proton-transfer reactions in the transient negative ions limit the release of bromine anions. [ABSTRACT FROM AUTHOR]

We employ the Tight Binding Fishbone-Wire Model to study the electronic structure and coherent transfer of a hole (the absence of an electron created by oxidation) in all possible ideal B-DNA dimers as well as in homopolymers (one base pair repeated along the whole sequence with purine on purine). The sites considered are the base pairs and the deoxyriboses, with no backbone disorder. For the time-independent problem, we calculate the eigenspectra and the density of states. For the time-dependent problem after oxidation (i.e., the creation of a hole either at a base pair or at a deoxyribose), we calculate the mean-over-time probabilities to find the hole at each site and establish the frequency content of coherent carrier transfer by computing the Weighted Mean Frequency at each site and the Total Weighted Mean Frequency of a dimer or polymer. We also evaluate the main oscillation frequencies of the dipole moment along the macromolecule axis and the relevant amplitudes. Finally, we focus on the mean transfer rates from an initial site to all others. We study the dependence of these quantities on the number of monomers that are used to construct the polymer. Since the value of the interaction integral between base pairs and deoxyriboses is not well-established, we treat it as a variable and examine its influence on the calculated quantities. [ABSTRACT FROM AUTHOR]

The Earth's atmosphere plays a critical role in transporting and dispersing biological aerosols. Nevertheless, the amount of microbial biomass in suspension in the air is so low that it is extremely difficult to monitor the changes over time in these communities. Real-time genomic studies can provide a sensitive and rapid method for monitoring changes in the composition of bioaerosols. However, the low abundance of deoxyribose nucleic acid (DNA) and proteins in the atmosphere, which is of the order of the contamination produced by operators and instruments, poses a challenge for the sampling process and the analyte extraction. In this study, we designed an optimized, portable, closed bioaerosol sampler based on membrane filters using commercial off-the-shelf components, demonstrating its end-to-end operation. This sampler can operate autonomously outdoors for a prolonged time, capturing ambient bioaerosols and avoiding user contamination. We first performed a comparative analysis in a controlled environment to select the optimal active membrane filter based on its ability to capture and extract DNA. We have designed a bioaerosol chamber for this purpose and tested three commercial DNA extraction kits. The bioaerosol sampler was tested outdoors in a representative environment and run for 24 h at 150 L/min. Our methodology suggests that a 0.22-µm polyether sulfone (PES) membrane filter can recover up to 4 ng of DNA in this period, sufficient for genomic applications. This system, along with the robust extraction protocol, can be automated for continuous environmental monitoring to gain insights into the time evolution of microbial communities within the air. [ABSTRACT FROM AUTHOR]

The unzipping of a double stranded DNA whose ends are subjected to a time dependent periodic force with frequency ω and amplitude G is studied using Monte Carlo simulations. We obtain the dynamical order parameter, Q, defined as the time average extension between the end monomers of two strands of the DNA over a period, and its probability distributions P(Q) at various force amplitudes and frequencies. We also study the time autocorrelations of extension and the dynamical order parameter for various chain lengths. The equilibrium force-distance isotherms were also obtained at various frequencies by using nonequilibrium work measurements. [ABSTRACT FROM AUTHOR]

The rapid improvements in identifying the genetic factors contributing to facial morphology have enabled the early identification of craniofacial syndromes. Similarly, this technology can be vital in forensic cases involving human identification from biological traces or human remains, especially when reference samples are not available in the deoxyribose nucleic acid (DNA) database. This review summarizes the currently used methods for predicting human phenotypes such as age, ancestry, pigmentation, and facial features based on genetic variations. To identify the facial features affected by DNA, various two-dimensional (2D)- and three-dimensional (3D)-scanning techniques and analysis tools are reviewed. A comparison between the scanning technologies is also presented in this review. Face-landmarking techniques and face-phenotyping algorithms are discussed in chronological order. Then, the latest approaches in genetic to 3D face shape analysis are emphasized. A systematic review of the current markers that passed the threshold of a genome-wide association (GWAS) of single nucleotide polymorphism (SNP)-face traits from the GWAS Catalog is also provided using the preferred reporting items for systematic reviews and meta-analyses (PRISMA), approach. Finally, the current challenges in forensic DNA phenotyping are analyzed and discussed. [ABSTRACT FROM AUTHOR]

Glycyrrhizin, a bioactive constituent of Glycyrrhiza glabra has been reported to ameliorate diabetes. Here, the effects of liposome-encapsulated glycyrrhizin on STZ-induced diabetes and associated oxidative stress were investigated. Wistar rats were grouped as control (NC, received placebo), diabetic (DC, STZ-induced), diabetic treated with free glycyrrhizin (DTG, 3 i.v. doses, 1.6 mg/0.5 ml), empty liposomes (DTl, 3 i.v. doses), and liposome-encapsulated glycyrrhizin (DTbd, 3 i.v. doses, 1.6 mg/0.5 ml). Serum glucose, insulin, intraperitoneal glucose tolerance test and glycohemoglobin were estimated. Free iron and iron-mediated oxidative stress were examined. Histological examinations of the kidney and liver were performed. Liposomal-glycyrrhizin treatment caused significant improvement of hyperglycemia (DC vs. DTbd p <.05), glucose intolerance (DC vs. DTG p <.01 and DC vs. DTbd p <.05), insulin (DC vs. DTG p <.1, DTbd vs. DC p <.05 and DTbd vs. DTG p <.1) and glycohemoglobin (DC vs. DTG p <.1 and DC vs. DTbd p <.05) levels in the DTbd group. Alleviation of free iron release (DC vs. DTbd p <.05), lipid peroxidation (DC + H2O2 vs. DTbd + H2O2p <.05), deoxyribose (DC + H2O2 vs. DTbd + H2O2, p <.05), and DNA degradation occurred in the DTbd group. The abnormalities of the kidney and liver were abolished in the DTbd group. The inhibitory effects were more pronounced compared to free glycyrrhizin. Liposome-encapsulated glycyrrhizin treatment caused inhibition of diabetic complications through its antioxidant effects and can be exploited for effective treatment of diabetes. [ABSTRACT FROM AUTHOR]

Trichomonas vaginalis is the causative agent of one of the most widespread sexually transmitted diseases in the world. The adhesion of the parasite to the vaginal epithelial cells is mediated by specific proteins and by a complex glycan structure, the lipoglycan (TvLG), which covers the pathogen surface. L-rhamnose is an important component of TvLG, comprising up to 40% of the monosaccharides. Thus, the inhibition of its production could lead to a severe alteration in the TvLG structure, making the L-rhamnose biosynthetic pathway an attractive pharmacologic target. We report the identification and characterization of the first committed and limiting step of the L-rhamnose biosynthetic pathway, UDP-D-glucose 4,6-dehydratase (UGD, EC 4.2.1.76). The enzyme shows a strong preference for UDP-D-glucose compared to dTDP-D-glucose; we propose that the mechanism underlying the higher affinity for the UDP-bound substrate is mediated by the differential recognition of ribose versus the deoxyribose of the nucleotide moiety. The identification of the enzymes responsible for the following steps of the L-rhamnose pathway (epimerization and reduction) was more elusive. However, sequence analyses suggest that in T. vaginalis L-rhamnose synthesis proceeds through a mechanism different from the typical eukaryotic pathways, displaying intermediate features between the eukaryotic and prokaryotic pathways and involving separate enzymes for the epimerase and reductase activities, as observed in bacteria. Altogether, these results form the basis for a better understanding of the formation of the complex glycan structures on TvLG and the possible use of L-rhamnose biosynthetic enzymes for the development of selective inhibitors. [ABSTRACT FROM AUTHOR]

As a common heavy metal contaminant, Cd2+ has adverse effects on food safety and consumer health. It is very important for human health to realize highly sensitive Cd2+ detection methods. The self-powered sensing system based on enzyme biofuel cells (EBFCs) does not need an external power supply, which can simplify the experimental equipment and has great application value in portable detection. Thus, the biosensor is innovatively integrated into the screen-printed electrode to construct a new type of portable sensor suitable for on-site and real-time Cd2+ detection. Hybridization chain reaction (HCR) combined with the Cd2+-dependent deoxyribose (DNAzyme) signal amplification strategy is used to enhance the detection sensitivity while specifically recognizing the Cd2+. Moreover, the self-powered sensor combines with smartphones to realize quantitative Cd2+ detection without other instruments and has the characteristic of Effectively improving the hazard detection technology is essential to ensure food safety. Portability, simplicity, and speed are suitable for real-time Cd2+ detection in the field. The dual mechanism and three quantitative modes combining colorimetric and two electrical signals output modes are adopted to realize the visualization and accurate detection. A series of research results confirm that this strategy is of great significance to strengthen the development of intelligent Cd2+ technology, expand the application of self-powered sensing technology, and improve the safety detection system. • Plug and play self-powered chip facilitates precision heavy metal detection. • Dual mechanism and three quantitative mode for quantitative analysis. • High sensitive detection chip can be used for Cd detection in tea samples. [ABSTRACT FROM AUTHOR]

We study transitions in intrinsically disordered regions (IDRs) upon complex formation, utilizing X-ray-solved structural dataset of protein-DNA and protein-RNA complexes, along with their available unbound protein forms. The identified IDRs are categorized into three classes: Disordered-to-Ordered (D-O), Disordered-to-Partial Ordered (D-PO) and Disordered-to-Disordered (D-D) after comparing them in unbound and complex forms. In the D-O class, IDRs form secondary structures like coils, helices, and strands upon binding to nucleic acids. Though a majority of these IDRs are present at the surface of the complexes, a significant number of IDRs are also observed at the interfaces and are involved in polar interactions. The hydrogen bonds made by the interface IDRs (B_IDRs) with phosphates and bases of nucleic acids are comparatively more than those formed with sugars. B_IDRs form more H-bonds with the ribose in protein-RNA than with the deoxyribose in protein-DNA. Among the B_IDRs, Arg and Lys prefer to interact with the major and minor grooves of DNA and RNA, respectively. Ser, however, prefers the minor groove in both the nucleic acids. Interestingly, we report 61 and 48 IDRs in 31 protein-DNA and 22 protein-RNA complexes, respectively, suggesting nucleic acid binding to proteins may also result in ordered-to-disordered transitions. [ABSTRACT FROM AUTHOR]

Heavy charged particles induce severe damage in DNA, which is a radiobiological advantage when treating radioresistant tumors. However, these particles can also induce cancer in humans exposed to them, such as astronauts in space missions. This damage can be directly induced by the radiation or indirectly by the attack of free radicals mainly produced by water radiolysis. We previously studied the impact of a proton on a DNA base pair, using the Time Dependent-Density Functional Theory (TD-DFT). In this work, we go a step further and study the attack of the OH· radical on the Guanine nucleotide to unveil how this molecule subsequently dissociates. The OH· attack on the H1′, H2′, H3′, and H5′ atoms in the guanine was investigated using the Ehrenfest dynamics within the TD-DFT framework. In all cases, the hydrogen abstraction succeeded, and the subsequent base pair dissociation was observed. The DNA dissociates in three major fragments: the phosphate group, the deoxyribose sugar, and the nitrogenous base, with slight differences, no matter which hydrogen atom was attacked. Hydrogen abstraction occurs at about 6 fs, and the nucleotide dissociation at about 100 fs, which agrees with our previous result for the direct proton impact on the DNA. These calculations may be a reference for adjusting reactive force fields so that more complex DNA structures can be studied using classical molecular dynamics, including both direct and indirect DNA damage. [ABSTRACT FROM AUTHOR]

DNA hydrogels have attracted increasing attention owing to their excellent permeability and high mechanical strength, together with thixotropy, versatile programmability and good biocompatibility. However, the moderate biostability and immune stimulation of DNA have arisen as big concerns for future potential clinical applications. Herein, we report the self‐assembly of a novel l‐DNA hydrogel, which inherited the extraordinary physical properties of a d‐DNA hydrogel. With the mirror‐isomer deoxyribose, this hydrogel exhibited improved biostability, withstanding fetal bovine serum (FBS) for at least 1 month without evident decay of its mechanical properties. The low inflammatory response of the l‐DNA hydrogel has been verified both in vitro and in vivo. Hence, this l‐DNA hydrogel with outstanding biostability and biocompatibility can be anticipated to serve as an ideal 3D cell‐culture matrix and implanted bio‐scaffold for long‐term biomedical applications. [ABSTRACT FROM AUTHOR]

DNA hydrogels have attracted increasing attention owing to their excellent permeability and high mechanical strength, together with thixotropy, versatile programmability and good biocompatibility. However, the moderate biostability and immune stimulation of DNA have arisen as big concerns for future potential clinical applications. Herein, we report the self‐assembly of a novel l‐DNA hydrogel, which inherited the extraordinary physical properties of a d‐DNA hydrogel. With the mirror‐isomer deoxyribose, this hydrogel exhibited improved biostability, withstanding fetal bovine serum (FBS) for at least 1 month without evident decay of its mechanical properties. The low inflammatory response of the l‐DNA hydrogel has been verified both in vitro and in vivo. Hence, this l‐DNA hydrogel with outstanding biostability and biocompatibility can be anticipated to serve as an ideal 3D cell‐culture matrix and implanted bio‐scaffold for long‐term biomedical applications. [ABSTRACT FROM AUTHOR]

The current study was designed to assess five species of the genus Phaseolus for phenolic content, flavonoid content, and antioxidant ability. The antioxidant capacity of the sample extracts was assessed using different antioxidant models such as ferric reducing antioxidant power (FRAP), DPPH free radical scavenging, phosphomolybdenum reducing power, ferrous ion chelating activity, hydrogen peroxide radical scavenging, hydroxyl radical scavenging, deoxyribose degradation, and ß-carotene bleaching assays. The results obtained discovered that the concentration of phenolics and flavonoids in the studied species ranged from 1.11 to 4.01mg TAE/g plant material and 0.11 to 1.16 mg QE/g plant material. The antioxidant activity of the extracts varied in a wide range in the different antioxidant assays depending on the genotype as well as the polarity of the solvents used to obtain the extracts. Ethanolic and aqueous extracts exhibited the maximum amount of phenolics and flavonoids among the solvents. The species studied exhibited a significant range of phenolics, flavonoids, and antioxidant capacity. Hence, the present investigation can provide a new direction by utilizing Phaseolus species to formulate cost-effective, eco-friendly, and valueadded therapeutic products. [ABSTRACT FROM AUTHOR]

Logic circuits based on DNA strand displacement reaction are the basic building blocks of future nanorobotic systems. The circuits tethered to DNA origami platforms present several advantages over solution-phase versions where couplings are always diffusion-limited. Here we consider a possible implementation of one of the basic operations needed in the design of these circuits, namely, signal replication. We show that with an appropriate preparation of the initial state, signal replication performs in a reproducible way. We also show the existence of side effects concomitant to the high effective concentrations in tethered circuits, such as slow leaky reactions and cross-activation. [ABSTRACT FROM AUTHOR]

Nonheme iron- and a-ketoglutarate (αKG)-dependent halogenases (NHFeHals), which catalyze the regio- and stereoselective halogenation of the unactivated C (sp3)-H bonds, exhibit tremendous potential in the challenging asymmetric halogenation. AdeV from Actinomadura sp. ATCC 39365 is the first identified carrier protein-free NHFeHal that catalyzes the chlorination of nucleotide 2'-deoxyadenosine-59-monophosphate (2'-dAMP) to afford 2'-chloro-2'-deoxyadenosine-5'-monophosphate. Here, we determined the complex crystal structures of AdeV/FeII/Cl and AdeV/FeII/Cl/αKG at resolutions of 1.76 and 1.74 Å, respectively. AdeV possesses a typical β-sandwich topology with H194, H252, αKG, chloride, and one water molecule coordinating FeII in the active site. Molecular docking, mutagenesis, and biochemical analyses reveal that the hydrophobic interactions and hydrogen bond network between the substrate-binding pocket and the adenine, deoxyribose, and phosphate moieties of 2'-dAMP are essential for substrate recognition. Residues H111, R177, and H192 might play important roles in the second-sphere interactions that control reaction partitioning. This study provides valuable insights into the catalytic selectivity of AdeV and will facilitate the rational engineering of AdeV and other NHFeHals for synthesis of halogenated nucleotides. [ABSTRACT FROM AUTHOR]

Catechin is an extensively investigated plant flavan-3-ol with a beneficial impact on human health that is often associated with antioxidant activities and iron coordination complex formation. The aim of this study was to explore these properties with FeII and FeIII using a combination of nanoelectrospray-mass spectrometry, differential pulse voltammetry, site-specific deoxyribose degradation assay, FeII autoxidation assay, and brine shrimp mortality assay. Catechin primarily favored coordination complex formation with Fe ions of the stoichiometry catechin:Fe in the ratio of 1:1 or 2:1. In the detected Fe–catechin coordination complexes, FeII prevailed. Differential pulse voltammetry, the site-specific deoxyribose degradation, and FeII autoxidation assays proved that coordination complex formation affected catechin's antioxidant effects. In situ formed Fe–catechin coordination complexes showed no toxic activities in the brine shrimp mortality assay. In summary, catechin has properties for the possible treatment of pathological processes associated with ageing and degeneration, such as Alzheimer's and Parkinson's diseases. [ABSTRACT FROM AUTHOR]

Absolute cross section (CS) data on the interaction of low energy electrons with DNA and its molecular constituents are required as input parameters in Monte-Carlo type simulations, for several radiobiological applications. Previously [V. Lemelin et al., J. Chem. Phys. 144, 074701 (2016)], we measured absolute vibrational CSs for low-energy electron scattering from condensed tetrahydrofuran, a convenient surrogate for the deoxyribose. Here we report absolute electronic CSs for energy losses of between 6 and 11.5 eV, by electrons with energies between 11 and 16 eV. The variation of these CSs with incident electron energy shows no evidence of transient anion states, consistent with theoretical and other experimental results, indicating that initial electron capture leading to DNA strand breaks occurs primarily on DNA bases or the phosphate group. [ABSTRACT FROM AUTHOR]

We probe the electrostatic cost associated with the approach phase of DNA translocation events. Within an analytical theory at the Debye-Huckel level, we calculate the electrostatic energy of a rigid DNA molecule interacting with a dielectric membrane. For carbon or silicon based low permittivity neutral membranes, the DNA molecule experiences a repulsive energy barrier between 10 kBT and 100 kBT. In the case of engineered membranes with high dielectric permittivities, the membrane surface attracts the DNA with an energy of the same magnitude. Both the repulsive and attractive interactions result from image-charge effects and their magnitude survive even for the thinnest graphene-based membranes of size d ≈ 6 Å. For weakly charged membranes, the electrostatic energy is always attractive at large separation distances but switches to repulsive close to the membrane surface. We also characterise the polymer length dependence of the interaction energy. For specific values of the membrane charge density, low permittivity membranes repel short polymers but attract long polymers. Our results can be used to control the strong electrostatic energy of DNA-membrane interactions prior to translocation events by chemical engineering of the relevant system parameters. [ABSTRACT FROM AUTHOR]

Daphne gnidium L. (Thymelaeaceae) has been used in the Mediterranean basin to treat skin diseases, rheumatism and toothache .Objective: the aim of this study was to evaluate the biological activities of butanol extract from the D. gnidium leaves. Methods: A quantitative analysis by high-performance liquid chromatography with a diode array detector (HPLC-DAD) was performed. The antioxidant activities were evaluated by using three different assays: 2,2-diphenyl-l-picrylhydrazyl assay (DPPH assay), deoxyribose degradation assay and Cellular Antioxidant Activity (CAA) assay. The butanol extract was investigated for anti-inflammatory and analgesic activities in animal models. In addition, its effect on the production of NO and lysosomal activity in vivo was assessed. Results: The HPLC-DAD analysis showed the presence of daphnetin. The butanol extract had a remarkable antioxidant activity in the different systems tested. Furthermore, it has an anti-inflammatory effect by inhibiting the xyleneinduced ear edema and reduced the number of abdominal constrictions in mice indicating analgesic effect. It also was found to inhibit (NO) production and lysosomal activity in vivo. Conclusion: These findings support the daphne use in traditional medicine for its analgesic and anti-inflammatory activities. Further investigations to elucidate its mechanism of action are required. [ABSTRACT FROM AUTHOR]

Earlier searches using DFT had identified two isomorphic H-bonded pyrimidine base pairs B1:B2 and B3:B4 as possible repeat units for macromolecular H-bonded duplexes with a capacity to store information as in DNA. This DFT study seeks to design repeat units with suitable backbones which can hold a sequence of base pairs in desired order. A deoxyribose phosphate backbone and a deoxyallopyranose phosphate backbone are proposed here. These sets of backboned nucleotide pairs are examined for their stability and their isomorphism. The results yield stable H-bonded nucleotide pairs with pairing energies of the order of those for the Watson-Crick DNA base pairs. Isomorphism is examined in the central pyrimidine base pair moiety, in the backbone torsional angles and in the overall topology. Out of three different sets of nucleotide pairs, the anionic deoxyribonucleotide pairs DA1:DA2 and DA3:DA4 emerge as showing the maximal overall isomorphism, while the pyranonucleotide pairs PyA1:PyA2 and PyA3:PyA4 are predicted as the most stable. [ABSTRACT FROM AUTHOR]

Culturing of Mycoplasma hominis in the presence of arginine and thymidine and subsequent comparative proteomic analysis of cells showed that, in addition to the already known arginine dihydrolase pathway of energy metabolism, M. hominis can utilize deoxyribose phosphates formed as a result of catabolism of pyrimidine nucleosides. In this case, a sharp deceleration of cell growth was observed. This allows M. hominis to occupy new niches in the host organism and survive under competitive conditions when the main sources of energy are unavailable. [ABSTRACT FROM AUTHOR]

The article reports that several state in the Union as well as the federal government passed some form of statute creating a right to post conviction DNA testing as several states limit the applicability of that right to certain groups of people. Topics include considered that Alabama courts as well as the United States Court of Appeals for the Eleventh Circuit17 have maintained that Rule 32 is the only mechanism to obtain DNA testing in non-capital cases.

DNA synthesis during homologous recombination is highly mutagenic and prone to template switches. Two‐ended DNA double‐strand breaks (DSBs) are usually repaired by gene conversion with a short patch of DNA synthesis, thus limiting the mutation load to the vicinity of the DSB. Single‐ended DSBs are repaired by break‐induced replication (BIR), which involves extensive and mutagenic DNA synthesis spanning up to hundreds of kilobases. It remains unknown how mutagenic BIR is suppressed at two‐ended DSBs. Here, we demonstrate that BIR is suppressed at two‐ended DSBs by proteins coordinating the usage of two ends of a DSB: (i) ssDNA annealing proteins Rad52 and Rad59 that promote second end capture, (ii) D‐loop unwinding helicase Mph1, and (iii) Mre11‐Rad50‐Xrs2 complex that promotes synchronous resection of two ends of a DSB. Finally, BIR is also suppressed when Sir2 silences a normally heterochromatic repair template. All of these proteins are particularly important for limiting BIR when recombination occurs between short repetitive sequences, emphasizing the significance of these mechanisms for species carrying many repetitive elements such as humans. Synopsis: While mutagenic break‐induced replication (BIR) repairs single‐ended DNA double‐strand breaks (DSBs), it needs to be suppressed at two‐ended breaks to ensure their faithful repair via gene conversion. Here, the coordinated usage of both DSB ends by ssDNA annealing and resection pathways is found to restrain unwanted BIR in budding yeast. Rad52‐ and Rad59‐mediated ssDNA annealing suppresses BIR by promoting second‐end capture.The Mre11‐Rad50‐Xrs2 complex suppresses BIR by promoting the synchronous formation of ssDNA at both ends of a break.ssDNA annealing is less important for DSB repair and preventing BIR when homology is long.Repair by BIR is not equally initiated at different genomic loci. [ABSTRACT FROM AUTHOR]

Simultaneous self-assembly of two distinct DNA origami nanostructures folded with the same scaffold strand was achieved in a single pot. Relative yields were tuned by adjusting concentrations of the competing strands, correlating well with folding kinetics of individual structures. These results can faciliate efficient fabrication of multi-structure systems and materials. [ABSTRACT FROM AUTHOR]

The dynamic interplay between two types of chiral structures; fully conjugated racemic hetero[7]helicenes and DNA strands prone to fold into G‐quadruplex structures is described. Both the [7]helicenes and the G‐quadruplex DNA structures exist in more than one conformation in solution. We show that the structures interact with and stabilise each other, mutually amplifying and stabilising certain conformations at increased temperatures. The [7]helicene ligands L1 and L2 stabilise the parallel conformation of k‐ras significantly, whereas hybrid (K+) and antiparallel (Na+) h‐telo G‐quadruplexes are stabilised upon conformational switching into altered G‐quadruplex conformations. Both L1 and L2 induce parallel G‐quadruplexes from hybrid structures (K+) and L1 induces hybrid G‐quadruplexes from antiparallel conformations (Na+). Enantioselective binding of one helicene enantiomer is observed for helicene ligand L2, and VTCD melting experiments are used to estimate the racemisation barrier of the helicene. [ABSTRACT FROM AUTHOR]

Purpose: The ERCC1-XPF 5'-3' DNA endonuclease complex is involved in the nucleotide excision repair pathway and in the DNA inter-strand crosslink repair pathway, two key mechanisms modulating the activity of chemotherapeutic alkylating agents in cancer cells. Inhibitors of the interaction between ERCC1 and XPF can be used to sensitize cancer cells to such drugs.Methods: We tested recently synthesized new generation inhibitors of this interaction and evaluated their capacity to sensitize cancer cells to the genotoxic activity of agents in synergy studies, as well as their capacity to inhibit the protein-protein interaction in cancer cells using proximity ligation assay.Results: Compound B9 showed the best activity being synergistic with cisplatin and mitomycin C in both colon and lung cancer cells. Also, B9 abolished the interaction between ERCC1 and XPF in cancer cells as shown by proximity ligation assay. Results of different compounds correlated with values from our previously obtained in silico predictions.Conclusion: Our results confirm the feasibility of the approach of targeting the protein-protein interaction between ERCC1 and XPF to sensitize cancer cells to alkylating agents, thanks to the improved binding affinity of the newly synthesized compounds. [ABSTRACT FROM AUTHOR]

Evidence suggests that the non-psychotropic phytocannabinoid cannabidiol (CBD) has anticancer activity on different cell lines and in animal models. The DNA-damaging drug epirubicin (EPI) is widely used for the treatment of malignant tumours. In this study we examined the effectiveness of CBD administered alone and in combination with EPI on HL-60, HL-60/Dox and MCF-7 cell-lines. We applied MTT reduction assay and the bioinformatics model of Chou-Talalay for experimental design of combination chemotherapy to evaluate the anticancer activity of several epirubicin-based combinations with CBD in various treatment regimens. In addition, we studied the efficacy of the co-treatment regimens to induce changes in two in-vitro model systems containing superoxide radical and 2-deoxyribose. We then evaluated the effectiveness of EPI plus CBD. The maximal growth cell inhibition ∼90% in leukemic and breast cancer cells was measured at the peak tested concentrations 2.5 EPI plus 25 CBD, µmol/L. The combination index (CI) value showed the presence of slightly expressed antagonism between EPI and CBD in most cases. The antiproliferative effect of the combination was reduced by only 8–10% vs. the inhibition induced by either EPI or CBD alone. We determined that the slight antagonism correlated positively to the registered dosage and decreased the extent of deoxyribose oxidative damage by using the enhanced chemiluminescent method with superoxide radicals. The therapeutic value of the combination of EPI plus CBD mainly consists of its high antiproliferative effect and the possibility to reduce the total dose on leukaemia-transformed cells by a factor of two. Supplemental data for this article is available online at https://doi.org/10.1080/13102818.2021.1996270. [ABSTRACT FROM AUTHOR]

HU, a DNA-binding protein, has a helical N-terminal region (NTR) of ∼44 residues and a beta strand- and IDR-rich C-terminal region (CTR) of ∼46 residues. CTR binds to DNA through (i) a clasp (two arginine/lysine-rich, IDR-rich beta hairpins that bind to phosphate groups in the minor groove), (ii) a flat surface (comprising four antiparallel beta strands that abut the major groove), and (iii) a charge cluster (two lysine residues upon a short C-terminal helix). HU forms a dimer displaying extensive inter-subunit CTR-CTR contacts. A single-chain simulacrum of these contacts (HU-Simul) incorporating all DNA-binding elements was created by fusing together the CTRs of Escherichia coli HU-A and Thermus thermophilus HU. HU-Simul is monomeric, binds to dsDNA and cruciform DNA, but not to ssDNA. • Construction of a novel, nature-inspired DNA-binding protein simulacrum, HU-Simul. • Autonomy of folding & assembly of the C-terminal domain of DNABII protein, HU. • Chimeric assembly of beta strands derived from HU sourced from different organisms. • Retention of dsDNA-binding ability but not ssDNA-binding ability in HU-Simul. • A thermostable DNA-binding protein through use of T. thermophilus beta strands. [ABSTRACT FROM AUTHOR]

The state complexity of a regular language L m is the number m of states in a minimal deterministic finite automaton (DFA) accepting L m . The state complexity of a regularity-preserving binary operation on regular languages is defined as the maximal state complexity of the result of the operation where the two operands range over all languages of state complexities ≤ m and ≤ n , respectively. We determine, for m ≥ 2 , n ≥ 3 , the exact value of the state complexity of the binary operation overlap assembly on regular languages. This operation was introduced by Csuhaj-Varjú, Petre, and Vaszil to model the process of self-assembly of two linear DNA strands into a longer DNA strand, provided that their ends "overlap". We prove that the state complexity of the overlap assembly of languages L m and L n , where m ≥ 2 and n ≥ 1 , is at most 2 (m − 1) 3 n − 1 + 2 n . Moreover, for m ≥ 2 and n ≥ 3 there exist languages L m and L n over an alphabet of size n whose overlap assembly meets the upper bound and this bound cannot be met with smaller alphabets. Finally, we prove that m + n is the state complexity of the overlap assembly in the case of unary languages and that there are binary languages whose overlap assembly has exponential state complexity at least m (2 n − 1 − 2) + 2. [ABSTRACT FROM AUTHOR]

DNA carries an inherent polymorphism, which surfaces under various external conditions. While B-form remains predominant under normal physiological conditions for most of the DNA sequences, low humidity and increased ion concentration cause B- to A-form transition. Certain proteins and molecules also sometimes cause local deformation of the DNA to the specific A-form. Previous experimental and computational studies focused on the overall B- to A-form transition. Here for the first time we investigated thermodynamics and mechanism of B- to A-form transition in water for various DNA sequences at a local dinucleotide base pair level. We introduced a new reaction coordinate Zp′, based on the unique order parameter Zp, to drive B- to A-form transition locally and thereby calculate free energy profiles for the same for all the ten different dinucleotide steps embedded in a twelve base pair DNA. Results show that the trend of 'A' and 'B' philicity observed in experiment is preserved even at this local dinucleotide level, indicating its localized origin. Higher free energy cost obtained here is attributed to the cost of creating B/A junctions along with formation of B->A transition at dimer level. We find that while water energetically stabilizes A-form for all the ten different dinucleotide steps to various extents, entropy acts against it. Therefore, we find that the stability of B-form DNA in water is entropic in origin. Mechanism of the conversion appears to be triggered by Slide; however, backbone parameters change concertedly. [ABSTRACT FROM AUTHOR]

Integrating dynamic DNA nanotechnology with protein‐controlled actuation will expand our ability to process molecular information. We have developed a strategy to actuate strand displacement reactions using DNA‐binding proteins by engineering synthetic DNA translators that convert specific protein‐binding events into trigger inputs through a programmed conformational change. We have constructed synthetic DNA networks responsive to two different DNA‐binding proteins, TATA‐binding protein and Myc‐Max, and demonstrated multi‐input activation of strand displacement reactions. We achieved protein‐controlled regulation of a synthetic RNA and of an enzyme through artificial DNA‐based communication, showing the potential of our molecular system in performing further programmable tasks. [ABSTRACT FROM AUTHOR]

Integrating dynamic DNA nanotechnology with protein‐controlled actuation will expand our ability to process molecular information. We have developed a strategy to actuate strand displacement reactions using DNA‐binding proteins by engineering synthetic DNA translators that convert specific protein‐binding events into trigger inputs through a programmed conformational change. We have constructed synthetic DNA networks responsive to two different DNA‐binding proteins, TATA‐binding protein and Myc‐Max, and demonstrated multi‐input activation of strand displacement reactions. We achieved protein‐controlled regulation of a synthetic RNA and of an enzyme through artificial DNA‐based communication, showing the potential of our molecular system in performing further programmable tasks. [ABSTRACT FROM AUTHOR]

MEF2 and NKX2–5 transcription factors interact with each other in cardiogenesis and are necessary for normal heart formation. Despite evidence suggesting that these two transcription factors function synergistically and possibly through direct physical interactions, molecular mechanisms by which they interact are not clear. Here we determined the crystal structures of ternary complexes of MEF2 and NKX2–5 bound to myocardin enhancer DNA in two crystal forms. These crystal structures are the first example of human MADS-box/homeobox ternary complex structures involved in cardiogenesis. Our structures reveal two possible modes of interactions between MEF2 and NKX2–5: MEF2 and NKX bind to adjacent DNA sites to recognize DNA in cis; and MEF2 and NKX bind to different DNA strands to interact with each other in trans via a conserved protein–protein interface observed in both crystal forms. Disease-related mutations are mapped to the observed protein–protein interface. Our structural studies provide a starting point to understand and further study the molecular mechanisms of the interactions between MEF2 and NKX2.5 and their roles in cardiogenesis. Unlabelled Image • First human MADS-box/homeobox ternary complex structures involved in cardiogenesis. • MEF2 and NKX2–5 interacts with each other in cis through DNA-mediated interaction or in trans through DNA and protein–protein mediated interaction. • Evolutionary conserved MEF2 and NKX2–5 protein–protein interaction interface was observed in two crystal forms. [ABSTRACT FROM AUTHOR]

Objective: Archived malaria rapid diagnostic test strips (mRDTs) serves as an important source of plasmodium Deoxyribose Nucleic Acid (DNA) in epidemiological studies. The presence of Plasmodium falciparum DNA (PfDNA) in mRDTs (yr. 2016-2017) and newly used ones (yr. 2018) were enumerated with a view to establish the parasite's optimum genomic DNA volume. Methods: A retrospective study to determine the yield and purity of used mRDTs was carried out on randomly selected mRDTs (2016 - 2018). Both positive and negative mRDTs samples were analyzed with nested Polymerase chain reaction (nPCR). Dried blood spots (DBS) were obtained from study enrolments and analyzed molecularly. nPCR and Agarose gel electrophoresis were used to determine P. falciparum DNA. Results: Agarose gel electrophoresis results showed that only 26 out of the 50 samples eligible for screening were PCR positive for P. falciparum. The following was observed; yrs.: 2016 - 17(34%) with 2.06 X 103 yield, 1.7235 purity; 2017 - 16(32%) with 1.03 X 103 yield, 1.7619 purity and 2018 - 17(34%) with 1.42 X 103 yield, 1.6194 purity. Molecular analysis (P.f. 18Ss rRNA) was determined to ascertain positive result that appeared negative using mRDTs or microscopy. The DNA yield of the DBS for 2018 was 1.66 X 103 and a purity (Optical Density 260/280) of 1.69. The purity was higher than that of the mRDTs with a DNA yield of 1.42 X 103 and 1.62 purity. Conclusion: PfDNA extraction is an important process for malaria PCR screening and the reliability is dependent on pureness and concentration. [ABSTRACT FROM AUTHOR]

A Y-type-DNA-functionalized nanogold probe was synthesized to identify telomerase and trigger drug release in cancer cells. This system involved a DNA-functionalized nanogold probe centered on gold nanoparticles with a dense modification of Y-type DNA molecular beacons on the surface. The Y-type DNA molecular beacons consisted of telomerase primers (TPs), a FAM-labeled single-strand DNA (Mismatch-DNA), and a single-strand DNA of two templates (Linker-DNA1 and Linker-DNA2). Doxorubicin (Dox), an anti-cancer drug molecule, was inserted into DNA double strands. When telomerase existed, TP was extended and the Mismatch-DNA was released, leading to the emission of fluorescent light from FAM while releasing Dox. This probe specifically detected cancer cells and did not affect normal cells. This drug delivery system will reduce the tumour size and cause minimal injury to normal tissues. [ABSTRACT FROM AUTHOR]

In oncology, some DNA intercalating agents have been used in chemotherapy for years to eradicate cancer cells, but these drugs generally suffer from a lack of selectivity for malignant tissues and consequently induce major side-effects. We report herein the design and synthesis of an antitumor intercalating agent ametantrone complemented with two identical peptide arms including a central Lys residue in order to selectively target palindromic sequences of DNA of malignant cells. The peptide arms are linked to the ametantrone core through 1,2,3-triazole. According to our docking prediction, this compound should be double-stranded β-sheet structured, and it has been designed to interact with two guanine residues upstream from a central d(CpG)2 intercalation site on each DNA strand, owing to the H-bonds involving the Lys terminal side chain ammonium group of the peptide arms. This new ametantrone derivative has been obtained thanks to a convergent synthetic pathway, whose key steps were double nucleophilic substitution performed on the ametantrone core, followed by "double-site" 1,3-dipolar cycloaddition affording the 1,4-disubstituted triazole linker almost quantitatively. Preliminary binding assays performed by mass spectrometry proved its accuracy for DNA palindromic sequences. The cytotoxicity of this compound was evaluated on three cancer cell lines and one healthy cell line, and compared to that of mitoxantone, a dihydroxylated analog of ametantrone. Such a peptide derivative was about ten-fold less cytotoxic than mitoxantrone on these cancer cell lines, but about fifty times less cytotoxic on healthy cells. This study could open new avenues towards the design of targeted intercalating agents. [ABSTRACT FROM AUTHOR]

Aiming at the detection of ultralow concentration target progesterone (Pro), a novel electrochemical aptasensor based on DNAzyme concatamers signal amplification strategy was proposed. The strategy consists of target DNA strands (TDNAs), and two different hairpin DNA molecules (H1 and H2). The signal is amplified by the large amount of DNAzyme. The TDNAs modified on the electrode open H1 structures in sequence and propagate a reaction of hybridization events between two alternating hairpins (H1and H2) to obtain abundant DNAzyme concatamers. Upon target Pro introduction, a specific Pro‐TDNAs reaction was executed, thereby resulting in the release of DNAzyme concatamers from the electrode. Subsequent differential pulse voltammetry(DPV) detection of aminoazobenzene (DAP) resulting by DNAzyme catalyze the oxidation of o‐phenylenediamine (OPD) with the aid of hydrogen peroxide (H2O2). Likewise, a small amount of target Pro can efficiently induce the release of a large number of the DNAzyme from the electrode in the form of DNAzyme concatamer. Under optimal conditions, the the proposed assay presents good electrochemical responses for determination of target Pro in the range of 0.5 to 15 ng/mL with the detection limit of 0.36 ng/mL. In addition, the resulting sensor can successfully distinguish Pro from coexisting interfering substance and show good stability and high repeatability. What's more, the methodology has also been demonstrated by assaying Pro‐spiked samples in serum. [ABSTRACT FROM AUTHOR]

In this paper, we present a coupled sine-Gordon (CSG) system, which describes the dynamics of two deoxyribonucleic acid (DNA) twisting strands in open configuration. We investigate the associated linear eigenvalue problem of the CSG system and obtain generalized formulae for multiple soliton solutions by employing the Darboux transformation (DT). Explicit expressions of one- and two-kink and line soliton solutions, single breather and first-order degenerate solutions are obtained by using particular solutions to the associated linear eigenvalue problem. We also present the dynamics of the different solutions. [ABSTRACT FROM AUTHOR]

8-Oxoguanine-DNA N-glycosylase (OGG1) is a eukaryotic DNA repair enzyme responsible for the removal of 8-oxoguanine (oxoG), one of the most abundant oxidative DNA lesions. OGG1 catalyzes two successive reactions - N-gly-cosidic bond hydrolysis (glycosylase activity) and DNA strand cleavage on the 3'-side of the lesion by ß-elimination (lyase activity). The enzyme also exhibits lyase activity with substrates containing apurinic/apyrimidinic (AP) sites (deoxyribose moieties lacking the nucleobase). OGG1 is highly specific for the base opposite the lesion, efficiently excising oxoG and cleaving AP sites located opposite to C, but not opposite to A. The activity is also profoundly decreased by amino acid changes that sterically interfere with oxoG binding in the active site of the enzyme after the lesion is everted from the DNA duplex. Earlier, the molecular dynamics approach was used to study the conformational dynamics of such human OGG1 mutants in complexes with the oxoG:C-containing substrate DNA, and the population density of certain conformers of two OGG1 catalytic residues, Lys249 and Asp268, was suggested to determine the enzyme activity. Here, we report the study of molecular dynamics of human OGG1 bound to the oxoG:A-containing DNA and OGG1 mutants bound to the AP:C-con-taining DNA. We showed that the enzyme low activity is associated with a decrease in the populations of Lys249 and Asp268 properly configured for catalysis. The experimentally measured rate constants for the OGG1 mutants show a good agreement with the models. We conclude that the enzymatic activity of OGG1 is determined majorly by the population density of the catalytically competent conformations of the active site residues Lys249 and Asp268. [ABSTRACT FROM AUTHOR]

A DNA G‐quadruplex adopting a (3+1) hybrid structure was modified in two adjacent syn positions of the antiparallel strand with anti‐favoring 2′‐deoxy‐2′‐fluoro‐riboguanosine (FrG) analogues. The two substitutions promoted a structural rearrangement to a topology with the 5′‐terminal G residue located in the central tetrad and the two modified residues linked by a V‐shaped zero‐nucleotide loop. Strikingly, whereas a sugar pucker in the preferred north domain is found for both modified nucleotides, the FrG analogue preceding the V‐loop is forced to adopt the unfavored syn conformation in the new quadruplex fold. Apparently, a preferred C3′‐endo sugar pucker within the V‐loop architecture outweighs the propensity of the FrG analogue to adopt an anti glycosidic conformation. Refolding into a V‐loop topology is likewise observed for a sequence modified at corresponding positions with two riboguanosine substitutions. In contrast, 2′‐F‐arabinoguanosine analogues with their favored south‐east sugar conformation do not support formation of the V‐loop topology. Examination of known G‐quadruplexes with a V‐shaped loop highlights the critical role of the sugar conformation for this distinct structural motif. [ABSTRACT FROM AUTHOR]