Search results for "Base Pairing"
showing 10 items of 22 documents
New insights into the mechanism of action of pyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-one derivatives endowed with anticancer potential
2018
Due to the scarce biological profile, the pyrazolo[1,2-a]benzo[1,2,3,4]tetrazine-3-one scaffold (PBT) has been recently explored as promising core for potential anticancer candidates. Several suitably decorated derivatives (PBTs) exhibited antiproliferative activity in the low-micromolar range associated with apoptosis induction and cell cycle arrest on S phase. Herein, we selected the most active derivatives and submitted them to further biological explorations to deepen the mechanism of action. At first, a DNA targeting is approached by means of flow Linear Dichroism experiments so as to evaluate how small planar molecules might interact with DNA, including the interference with the catal…
Singlet Oxygen Attack on Guanine: Reactivity and Structural Signature within the B-DNA Helix
2016
International audience; Oxidatively generated DNA lesions are numerous and versatile, and have been the subject of intensive research since the discovery of 8-oxoguanine in 1984. Even for this prototypical lesion, the precise mechanism of formation remains elusive due to the inherent difficulties in characterizing high-energy intermediates. We have probed the stability of the guanine endoperoxide in B-DNA as a key intermediate and determined a unique activation free energy of around 6 kcal mol−1 for the formation of the first C−O covalent bond upon the attack of singlet molecular oxygen (1O2) on the central guanine of a solvated 13 base-pair poly(dG-dC), described by means of quantum mechan…
Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease
2018
SUMMARY Maternally skewed transmission of traits has been associated with genomic imprinting and oocyte-derived mRNA. We report canine congenital eye malformations, caused by an amino acid deletion (K12del) near the N terminus of retinol-binding protein (RBP4). The disease is only expressed when both dam and offspring are deletion homozygotes. RBP carries vitamin A (retinol) from hepatic stores to peripheral tissues, including the placenta and developing eye, where it is required to synthesize retinoic acid. Gestational vitamin A deficiency is a known risk factor for ocular birth defects. The K12del mutation disrupts RBP folding in vivo, decreasing its secretion from hepatocytes to serum. T…
Manganese Ions Individually Alter the Reverse Transcription Signature of Modified Ribonucleosides
2020
Reverse transcription of RNA templates containing modified ribonucleosides transfers modification-related information as misincorporations, arrest or nucleotide skipping events to the newly synthesized cDNA strand. The frequency and proportion of these events, merged from all sequenced cDNAs, yield a so-called RT signature, characteristic for the respective RNA modification and reverse transcriptase (RT). While known for DNA polymerases in so-called error-prone PCR, testing of four different RTs by replacing Mg2+ with Mn2+ in reaction buffer revealed the immense influence of manganese chloride on derived RT signatures, with arrest rates on m1A positions dropping from 82% down to 24%. Additi…
Can copper(II) mediate Hoogsteen base-pairing in a left-handed DNA duplex? A pulse EPR study
2010
Pulse EPR spectroscopy is sued to investigate possible structural features of the copper(II) ion coordinated to poly(dG-dC) poly(dG-dC) in a frozen aqueous solution, and the structural change of the polynucleotide induced by the presence of the metal ion. Two different copper species were identified and their geometry explained by a molecular model. According to this model, one species is exclusively coordinated to a single guanine with the N7 nitrogen atom forming a coordinative bond with the copper. In the other species, a guanine and a cytosine form a ternary complex together with the copper ion. A copper crosslink between the N7 of guanine and N3 of cytosine is proposed as the most prob…
Detection of a new 3-base pair insertion mutation in the protease gene of human immunodeficiency virus type 1 during highly active antiretroviral the…
2005
To investigate a new insertion mutation in the protease (PR) gene of human immunodeficiency virus type 1 (HIV-1) in a patient extensively pretreated with antiretroviral drugs, genotypic analyses of plasma-derived viruses were performed by sequencing segments of 1302 nucleotides in the pol gene of HIV-1. Despite optimal compliance to highly active antiretroviral therapy (HAART) the patient showed poor virological success. Nucleotide sequences of retrospective available plasma samples exhibited a previously unknown 3-bp insertion mutation, corresponding to a leucine, between codons 31 and 32 of the PR gene. This kind of mutation appears to be very rare and it does not seem to be associated wi…
The selective synthesis of metallanucleosides and metallanucleotides: a new tool for the functionalization of nucleic acids.
2012
Nucleobases team up: the efficient and selective preparation of purine-derived metallanucleosides, metallanucleotides, and metalladinucleotides having M-C bonds (M=Ir(III), Rh(III)) is reported for the first time. The results presented may be applied to the synthesis of functionalized nucleic acids, or DNA/RNA-modified segments.
Dissipative lattice model with exact traveling discrete kink-soliton solutions: Discrete breather generation and reaction diffusion regime
1999
International audience; We introduce a nonlinear Klein-Gordon lattice model with specific double-well on-site potential, additional constant external force and dissipation terms, which admits exact discrete kink or traveling wave fronts solutions. In the nondissipative or conservative regime, our numerical simulations show that narrow kinks can propagate freely, and reveal that static or moving discrete breathers, with a finite but long lifetime, can emerge from kink-antikink collisions. In the general dissipative regime, the lifetime of these breathers depends on the importance of the dissipative effects. In the overdamped or diffusive regime, the general equation of motion reduces to a di…
DNA oxidation products determined with repair endonucleases in mammalian cells: Types, basal levels and influence of cell proliferation
1999
Purified repair endonucleases such as Fpg protein, endonuclease III and IV allow a very sensitive quantification of various types of oxidative DNA modifications in mammalian cells. By means of these assays, the numbers of base modifications sensitive to Fpg protein, which include 8-hydroxyguanine (8-oxoG), were determined to be less than 0.3 per 10(6) bp in several types of untreated cultured mammalian cells and human lymphocytes and less than 10 per 10(6) bp in mitochondrial DNA from rat and porcine liver. Oxidative 5,6-dihydropyrimidine derivatives sensitive to endonuclease III and sites of base loss sensitive to endonuclease IV or exonuclease III were much less frequent than Fpg-sensitiv…
Constitutive Promoter Occupancy by the MBF-1 Activator and Chromatin Modification of the Developmental Regulated Sea Urchin α-H2A Histone Gene
2007
The tandemly repeated sea urchin alpha-histone genes are developmentally regulated. These genes are transcribed up to the early blastula stage and permanently silenced as the embryos approach gastrulation. As previously described, expression of the alpha-H2A gene depends on the binding of the MBF-1 activator to the 5' enhancer, while down-regulation relies on the functional interaction between the 3' sns 5 insulator and the GA repeats located upstream of the enhancer. As persistent MBF-1 binding and enhancer activity are detected in gastrula embryos, we have studied the molecular mechanisms that prevent the bound MBF-1 from trans-activating the H2A promoter at this stage of development. Her…