scholarly journals Targeting the ALS/FTD-associated A-DNA kink with anthracene-based metal complex causes DNA backbone straightening and groove contraction

2021 ◽  
Author(s):  
Cyong-Ru Jhan ◽  
Roshan Satange ◽  
Shun-Ching Wang ◽  
Jing-Yi Zeng ◽  
Yih-Chern Horng ◽  
...  
Keyword(s):  
Hot Spot ◽  
Hydration Shell ◽  
Repeat Motif ◽  
Dna Duplex ◽  
Base Pairs ◽  
Dna And Rna ◽  
Detailed Structural Analysis ◽  
Small Molecule Compound ◽  
Dna Backbone ◽  
Locomotor Deficits

Abstract The use of a small molecule compound to reduce toxic repeat RNA transcripts or their translated aberrant proteins to target repeat-expanded RNA/DNA with a G4C2 motif is a promising strategy to treat C9orf72-linked disorders. In this study, the crystal structures of DNA and RNA–DNA hybrid duplexes with the -GGGCCG- region as a G4C2 repeat motif were solved. Unusual groove widening and sharper bending of the G4C2 DNA duplex A-DNA conformation with B-form characteristics inside was observed. The G4C2 RNA–DNA hybrid duplex adopts a more typical rigid A form structure. Detailed structural analysis revealed that the G4C2 repeat motif of the DNA duplex exhibits a hydration shell and greater flexibility and serves as a ‘hot-spot’ for binding of the anthracene-based nickel complex, NiII(Chro)2 (Chro = Chromomycin A3). In addition to the original GGCC recognition site, NiII(Chro)2 has extended specificity and binds the flanked G:C base pairs of the GGCC core, resulting in minor groove contraction and straightening of the DNA backbone. We have also shown that Chro-metal complexes inhibit neuronal toxicity and suppresses locomotor deficits in a Drosophila model of C9orf72-associated ALS. The approach represents a new direction for drug discovery against ALS and FTD diseases by targeting G4C2 repeat motif DNA.

Studies on the thymine–mercury–thymine base pairing in parallel and anti-parallel DNA duplexes

2015 ◽  
Vol 39 (11) ◽  
pp. 8752-8762 ◽  
Author(s):  
Gaofeng Liu ◽  
Zhiwen Li ◽  
Junfei Zhu ◽  
Yang Liu ◽  
Ying Zhou ◽  
...  
Keyword(s):  
Dna Duplexes ◽  
Base Pairing ◽  
Dna Duplex ◽  
Base Pairs ◽  
Thermal Stabilities

Parallel and anti-parallel T–Hg–T base pairs have different thermal stabilities and conformational influences on DNA duplex structures.

scholarly journals Isolation of RNA from a mixture and its detection by utilizing a microgel-based optical device

2018 ◽  
Vol 96 (12) ◽  
pp. 1079-1086 ◽  
Author(s):  
Molla R. Islam ◽  
Shakiba Azimi ◽  
Faranak Teimoory ◽  
Glen Loppnow ◽  
Michael J. Serpe
Keyword(s):  
Melting Temperature ◽  
Magnetic Beads ◽  
Colorimetric Detection ◽  
Optical Devices ◽  
High Melting ◽  
Dna Duplex ◽  
Dna And Rna ◽  
High Melting Temperature ◽  
Hybrid Duplex ◽  
Fluorescent Studies

In this investigation, we show that RNA can be separated from a solution containing DNA and RNA and the isolated RNA can be detected using poly (N-isopropylacrylamide-co-N-(3-aminopropyl) methacrylamide hydrochloride) microgel-based optical devices (etalons). The isolation of RNA was accomplished by using hairpin-functionalized magnetic beads (MMPDNA) and differential melting, based on the fact that the DNA–RNA hybrid duplex is stronger (i.e., high melting temperature) than the DNA–DNA duplex (i.e., low melting temperature). By performing concurrent etalon sensing and fluorescent studies, we found that the MMPDNA combined with differential melting was capable of selectively separating RNA from DNA. This selective separation and simple colorimetric detection of RNA from a mixture will help lead to future RNA-based disease diagnostic devices.

scholarly journals Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation

2010 ◽  
Vol 2010 ◽  
pp. 1-4 ◽  
Author(s):  
Regina R. Monaco
Keyword(s):  
External Surface ◽  
Computational Study ◽  
Helical Axis ◽  
Base Pairs ◽  
Bond Rotation ◽  
Double Stranded Dna ◽  
Dna Backbone ◽  
Interaction Measure ◽  
The Creation ◽  
A Site

The mechanism of intercalation and the ability of double stranded DNA (dsDNA) to accommodate a variety of ligands in this manner has been well studied. Proposed mechanistic steps along this pathway for the classical intercalator ethidium have been discussed in the literature. Some previous studies indicate that the creation of an intercalation site may occur spontaneously, with the energy for this interaction arising either from solvent collisions or soliton propagation along the helical axis. A subsequent 1D diffusional search by the ligand along the helical axis of the DNA will allow the ligand entry to this intercalation site from its external, electrostatically stabilized position. Other mechanistic studies show that ethidium cation participates in the creation of the site, as a ligand interacting closely with the external surface of the DNA can cause unfavorable steric interactions depending on the ligands' orientation, which are relaxed during the creation of an intercalation site. Briefly, such a site is created by the lengthening of the DNA molecule via bond rotation between the sugars and phosphates along the DNA backbone, causing an unwinding of the dsDNA itself and separation between the adjacent base pairs local to the position of the ligand, which becomes the intercalation site. Previous experimental measurements of this interaction measure the enthalpic cost of this part of the mechanism to be about −8 kcal/mol. This paper reports the observation, during a computational study, of the spontaneous opening of an intercalation site in response to the presence of a single ethidium cation molecule in an externally bound configuration. The concerted motions between this ligand and the host, a dsDNA decamer, are clear. The dsDNA decamer AGGATGCCTG was studied; the central site was the intercalation site.

scholarly journals Comparison of Whole Plastome Sequences between Thermogenic Skunk Cabbage Symplocarpus renifolius and Nonthermogenic S. nipponicus (Orontioideae; Araceae) in East Asia

2019 ◽  
Vol 20 (19) ◽  
pp. 4678 ◽  
Author(s):  
Seon-Hee Kim ◽  
JiYoung Yang ◽  
Jongsun Park ◽  
Takayuki Yamada ◽  
Masayuki Maki ◽  
...  
Keyword(s):  
Hot Spot ◽  
Evolutionary Relationship ◽  
Early Spring ◽  
Base Pairs ◽  
Complete Chloroplast Genome ◽  
Noncoding Regions ◽  
Species Pairs ◽  
Skunk Cabbage ◽  
Basal Position ◽  
Simple Sequence

Symplocarpus, a skunk cabbage genus, includes two sister groups, which are drastically different in life history traits and thermogenesis, as follows: The nonthermogenic summer flowering S. nipponicus and thermogenic early spring flowering S. renifolius. Although the molecular basis of thermogenesis and complete chloroplast genome (plastome) of thermogenic S. renifolius have been well characterized, very little is known for that of S. nipponicus. We sequenced the complete plastomes of S. nipponicus sampled from Japan and Korea and compared them with that of S. renifolius sampled from Korea. The nonthermogenic S. nipponicus plastomes from Japan and Korea had 158,322 and 158,508 base pairs, respectively, which were slightly shorter than the thermogenic plastome of S. renifolius. No structural or content rearrangements between the species pairs were found. Six highly variable noncoding regions (psbC/trnS, petA/psbJ, trnS/trnG, trnC/petN, ycf4/cemA, and rpl3/rpl22) were identified between S. nipponicus and S. renifolius and 14 hot-spot regions were also identified at the subfamily level. We found a similar total number of SSR (simple sequence repeat) motifs in two accessions of S. nipponicus sampled from Japan and Korea. Phylogenetic analysis supported the basal position of subfamily Orontioideae and the monophyly of genus Symplocarpus, and also revealed an unexpected evolutionary relationship between S. nipponicus and S. renifolius.

scholarly journals Involvement of Sir2/4 in Silencing of DNA Breakage and Recombination on Mouse YACs during Yeast Meiosis

2005 ◽  
Vol 16 (3) ◽  
pp. 1449-1455 ◽  
Author(s):  
Yair Klieger ◽  
Ofer Yizhar ◽  
Drora Zenvirth ◽  
Neta Shtepel-Milman ◽  
Margriet Snoek ◽  
...  
Keyword(s):  
Meiotic Recombination ◽  
Hot Spot ◽  
Yeast Cells ◽  
Class Iii ◽  
Dna Double Strand Breaks ◽  
Artificial Chromosomes ◽  
Mouse Major Histocompatibility Complex ◽  
Dna Backbone ◽  
Yeast Meiosis ◽  
Yeast Artificial Chromosomes

Yeast artificial chromosomes (YACs) that contain human DNA backbone undergo DNA double-strand breaks (DSBs) and recombination during yeast meiosis at rates similar to the yeast native chromosomes. Surprisingly, YACs containing DNA covering a recombination hot spot in the mouse major histocompatibility complex class III region do not show meiotic DSBs and undergo meiotic recombination at reduced levels. Moreover, segregation of these YACs during meiosis is seriously compromised. In meiotic yeast cells carrying the mutations sir2 or sir4, but not sir3, these YACs show DSBs, suggesting that a unique chromatin structure of the YACs, involving Sir2 and Sir4, protects the YACs from the meiotic recombination machinery. We speculate that the paucity of DSBs and recombination events on these YACs during yeast meiosis may reflect the refractory nature of the corresponding region in the mouse genome.

5-Hydroxyuracil can form stable base pairs with all four bases in a DNA duplex

2005 ◽  
pp. 400 ◽  
Author(s):  
Varatharasa Thiviyanathan ◽  
Anoma Somasunderam ◽  
David E. Volk ◽  
David G. Gorenstein
Keyword(s):  
Dna Duplex ◽  
Base Pairs

scholarly journals Crystal structure of a DNA duplex containing four Ag(i) ions in consecutive dinuclear Ag(i)-mediated base pairs: 4-thiothymine–2Ag(i)–4-thiothymine

2017 ◽  
Vol 53 (86) ◽  
pp. 11747-11750 ◽  
Author(s):  
Jiro Kondo ◽  
Toru Sugawara ◽  
Hisao Saneyoshi ◽  
Akira Ono
Keyword(s):  
Crystal Structure ◽  
Crystal Structures ◽  
Dna Duplexes ◽  
Dna Duplex ◽  
Base Pairs

The crystal structures of 4-thiothymine–2AgI–4-thiothymine base pairs in B-form DNA duplexes have been solved.

scholarly journals 2P133 Spectroscopic analysis of DNA duplex including T-Hg-T base pairs

2005 ◽  
Vol 45 (supplement) ◽  
pp. S153
Author(s):  
S. Oda ◽  
H. Yamaguchi ◽  
A. Ono ◽  
C. Kojima ◽  
Y. Kondo ◽  
...  
Keyword(s):  
Spectroscopic Analysis ◽  
Dna Duplex ◽  
Base Pairs

scholarly journals The accidental ally: Nucleosomal barriers can accelerate cohesin mediated loop formation in chromatin

2019 ◽  
Author(s):  
Ajoy Maji ◽  
Ranjith Padinhateeri ◽  
Mithun K. Mitra
Keyword(s):  
Effective Diffusion ◽  
Diffusion Constant ◽  
Loop Formation ◽  
Base Pairs ◽  
Diffusion Constants ◽  
Dna Backbone ◽  
The Mean ◽  
The Times ◽  
Lower Loop ◽  
Kinetics Of

AbstractAn important question in the context of the 3D organization of chromosomes is the mechanism of formation of large loops between distant base pairs. Recent experiments suggest that the formation of loops might be mediated by Loop Extrusion Factor proteins like cohesin. Experiments on cohesin have shown that cohesins walk diffusively on the DNA, and that nucleosomes act as obstacles to the diffusion, lowering the permeability and hence reducing the effective diffusion constant. An estimation of the times required to form the loops of typical sizes seen in Hi-C experiments using these low effective diffusion constants leads to times that are unphysically large. The puzzle then is the following, how does a cohesin molecule diffusing on the DNA backbone achieve speeds necessary to form the large loops seen in experiments? We propose a simple answer to this puzzle, and show that while at low densities, nucleosomes act as barriers to cohesin diffusion, beyond a certain concentration, they can reduce loop formation times due to a subtle interplay between the nucleosome size and the mean linker length. This effect is further enhanced on considering stochastic binding kinetics of nucleosomes on the DNA backbone, and leads to predictions of lower loop formation times than might be expected from a naive obstacle picture of nucleosomes.

scholarly journals The biofilm matrix scaffold of Pseudomonas species contains non-canonically base paired extracellular DNA and RNA

2019 ◽  
Author(s):  
Thomas Seviour ◽  
Fernaldo Richtia Winnerdy ◽  
Lan Li Wong ◽  
Xiangyan Shi ◽  
Sudarsan Mugunthan ◽  
...  
Keyword(s):  
Viscoelastic Properties ◽  
Extracellular Dna ◽  
Chromosomal Dna ◽  
Base Pairs ◽  
Matrix Component ◽  
Dna And Rna ◽  
Pseudomonas Species ◽  
The Matrix ◽  
Nucleic Acid Conformation ◽  
Biofilm Matrix

AbstractWhile extracellular DNA (eDNA) is recognized as a critical biofilm matrix component, it is not understood how it contributes to biofilm function. Here we isolate eDNA from Pseudomonas biofilms using ionic liquids, and discover that its key biophysical signatures, i.e. fluid viscoelasticity, nucleic acid conformation, and temperature and pH dependencies of gel to solution transitions, are maintained. Solid-state analysis of isolated eDNA, as a proxy for eDNA structure in biofilms, revealed non-canonical Hoogsteen base pairs, triads or tetrads involving guanine and thymine or uracil. These were less abundant in chromosomal DNA and undetected as eDNA underwent gel-sol transition. Purine-rich RNA was present in the eDNA network, which potentially enables eDNA to be the main cross-linking exopolymer in the matrix through non-canonical nucleobase interactions. Our study suggests that Pseudomonas assemble extracellular DNA and RNA into a network with viscoelastic properties, which underpin their persistence and spreading, and may aid the development of more effective controls for biofilm-associated infections.

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