Intercalation into the DNA double helix and in vivo biological activity of water-soluble planar [Pt(diimine)(N,N-dihydroxyethyl-N′-benzoylthioureato)]+Cl− complexes: A study of their thermal stability, their CD spectra and their gel mobility

2005 ◽  
Vol 440 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Yu-Shan Wu ◽  
Klaus R. Koch ◽  
Valerie R. Abratt ◽  
Horst H. Klump
Keyword(s):  
Thermal Stability ◽  
Biological Activity ◽  
Double Helix ◽  
Water Soluble ◽  
Cd Spectra ◽  
Dna Double Helix

scholarly journals Bases alternatives et organismes synthétiques

2018 ◽  
Vol 34 (2) ◽  
pp. 179-182 ◽  
Author(s):  
Bertrand Jordan
Keyword(s):  
Amino Acids ◽  
Unnatural Amino Acids ◽  
Double Helix ◽  
Dna Double Helix

Alternative bases that can fit into the DNA double helix have now been used in vivo to direct the synthesis of proteins incorporating unnatural amino acids. This bioengineering feat is significant at both the conceptual and the practical levels

scholarly journals Potential for measurement of the distribution of DNA folds in complex environments using Correlated X-ray Scattering

2016 ◽  
Vol 30 (08) ◽  
pp. 1650117 ◽  
Author(s):  
Gundolf Schenk ◽  
Brad Krajina ◽  
Andrew Spakowitz ◽  
Sebastian Doniach
Keyword(s):  
Metallic Nanoparticles ◽  
Double Helix ◽  
X Rays ◽  
Complex Environments ◽  
Length Scales ◽  
X Ray ◽  
X Ray Scattering ◽  
Dna Double Helix ◽  
Ray Scattering

In vivo chromosomal behavior is dictated by the organization of genomic DNA at length scales ranging from nanometers to microns. At these disparate scales, the DNA conformation is influenced by a range of proteins that package, twist and disentangle the DNA double helix, leading to a complex hierarchical structure that remains undetermined. Thus, there is a critical need for methods of structural characterization of DNA that can accommodate complex environmental conditions over biologically relevant length scales. Based on multiscale molecular simulations, we report on the possibility of measuring supercoiling in complex environments using angular correlations of scattered X-rays resulting from X-ray free electron laser (xFEL) experiments. We recently demonstrated the observation of structural detail for solutions of randomly oriented metallic nanoparticles [D. Mendez et al., Philos. Trans. R. Soc. B 360 (2014) 20130315]. Here, we argue, based on simulations, that correlated X-ray scattering (CXS) has the potential for measuring the distribution of DNA folds in complex environments, on the scale of a few persistence lengths.

scholarly journals The deaminase ADAL-pivoted catabolism checkpoint suppresses aberrant DNA N6-methyladenine incorporation

2021 ◽  
Author(s):  
Shaokun Chen ◽  
Weiyi Lai ◽  
Zhiyi Zhao ◽  
Ning Zhang ◽  
Yan Liu ◽  
...  
Keyword(s):  
Adenylate Kinase ◽  
Patient Survival ◽  
Double Helix ◽  
Intracellular Degradation ◽  
Dna Double Helix ◽  
Adenylate Kinase 1 ◽  
Phosphorylation Rate

Abstract Abundant RNA N6-methyladenine (m6A) is degraded in RNA decay and potentially induces aberrant DNA N6-methyladenine (6mA) misincorporation. Biophysically, like truly methylated product DNA 6mA, misincorporated 6mA also destabilizes the DNA double helix and thus ditto affects DNA replication and transcription. By heavy stable isotope tracing, we demonstrate that intracellular degradation of RNA m6A cannot induce any misincorporated DNA 6mA, unveiling the existence of a catabolism checkpoint that blocks DNA 6mA misincorporation. We further show that the deaminase ADAL preferentially catabolizes N6-methyl-2’-deoxyadenosine monophosphate (6mdAMP) in vitro and in vivo, and adenylate kinase 1 restricts the phosphorylation rate of 6mdAMP, together contributing to the identified checkpoint. Noteworthy, low ADAL expression reduces dramatically the patient survival in four cancers. Collectively, our data strongly support a pivotal role of ADAL in the suppression of 6mA misincorporation and implicate that both ADAL and misincorporated 6mA may mark cancer abnormalities.

scholarly journals Protective effects of orally applied fullerenol nano particles in rats after a single dose of doxorubicin

2011 ◽  
Vol 65 (3) ◽  
pp. 329-337 ◽  
Author(s):  
Ivana Icevic ◽  
Aleksandar Vukmirovic ◽  
Branislava Srdjenovic ◽  
Jan Sudji ◽  
Aleksandar Djordjevic ◽  
...  
Keyword(s):  
Biological Activity ◽  
Single Dose ◽  
Antioxidant Properties ◽  
Water Soluble ◽  
Nano Particles ◽  
Protective Effects ◽  
In Vivo Models ◽  
Nephroprotective Effect

Polyhydroxylated, water soluble, fullerenol C60(OH)24 nano particles (FNP) in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX) (8 mg/kg (i.p.)) 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP), in H2O:DMSO (80:20, w/w) solution given orally in final doses of 10, 14.4, and 21.2 mg/kg three days successively, has the protective (hepatoprotective and nephroprotective) effect against doxorubicin-induced cytotoxicity via its antioxidant properties.

ABSENCE OF OESTRADIOL-17β DEHYDROGENASE FROM THE PROGESTERONE-DOMINATED MOUSE UTERUS

1980 ◽  
Vol 85 (1) ◽  
pp. 155-159 ◽  
Author(s):  
B. F. CLARK
Keyword(s):  
Biological Activity ◽  
Water Soluble ◽  
Human Endometrium ◽  
Mouse Uterus ◽  
Uterine Lumen ◽  
Ovariectomized Mice ◽  
Metabolic Conversion

SUMMARY In the mouse uterus the development of sensitivity to a decidualizing stimulus requires large amounts of progesterone and small amounts of oestradiol-17β. During this process progesterone induces changes in the sensitivity of the tissues of the uterus to oestrogen. From observations of human endometrium it has been suggested that progesterone modulates the biological activity of oestradiol-17β by stimulating the metabolic conversion of oestradiol-17β to oestrone. Accordingly [6,7-3H]oestradiol-17β was injected subcutaneously into ovariectomized mice at various stages of the development of sensitivity to a decidualizing injection of oil into the uterine lumen. Radioactivity was extracted 4 h later, fractionated and identified. There was no alteration in the amounts of oestradiol, oestrone or water-soluble metabolites in the uteri whether the mice were treated with progesterone or with progesterone plus oestrogen or whether the uterine horns were decidualized for 24 or 48 h. The results suggest that in vivo the metabolism of oestradiol-17β by the uterus is not stimulated by progesterone.

scholarly journals Activation of p53 Function by Human Transcriptional Coactivator PC4: Role of Protein-Protein Interaction, DNA Bending, and Posttranslational Modifications

2007 ◽  
Vol 27 (21) ◽  
pp. 7603-7614 ◽  
Author(s):  
Kiran Batta ◽  
Tapas K. Kundu
Keyword(s):  
Dna Binding ◽  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Double Helix ◽  
Dna Bending ◽  
Cell Cycle Checkpoints ◽  
Transcriptional Coactivator ◽  
Dna Double Helix

ABSTRACT Tumor suppressor p53 controls cell cycle checkpoints and apoptosis via the transactivation of several genes that are involved in these processes. The functions of p53 are regulated by a wide variety of proteins, which interact with it either directly or indirectly. The multifunctional human transcriptional coactivator PC4 interacts with p53 in vivo and in vitro and regulates its function. Here we report the molecular mechanisms of the PC4-mediated activation of p53 function. PC4 interacts with the DNA binding and C-terminal domains of p53 through its DNA binding domain, which is essential for the stimulation of p53 DNA binding. Remarkably, ligation-mediated circularization assays reveal that PC4 induces significant bending in the DNA double helix. Deletion mutants defective in DNA bending are found to be impaired in activating p53-mediated DNA binding and apoptosis. Furthermore, acetylation of PC4 enhances, while phosphorylation abolishes, its ability to bend DNA, activate p53 DNA binding, and, thereby, regulate p53 functions. In conclusion, PC4 activates p53 recruitment to p53-responsive promoters (Bax and p21) in vivo through its interaction with p53 and by providing bent substrate for p53 recruitment. These results elucidate the general molecular mechanisms of activation of p53 function, mediated by its coactivators.

scholarly journals Cross-linked growth hormone dimers have enhanced biological activity

1998 ◽  
pp. 449-459 ◽  
Author(s):  
JW Mockridge ◽  
R Aston ◽  
DJ Morrell ◽  
AT Holder
Keyword(s):  
Growth Hormone ◽  
Biological Activity ◽  
Costal Cartilage ◽  
Human Growth ◽  
Water Soluble ◽  
Significant Enhancement ◽  
Cross Linking ◽  
Sds Page ◽  
Snell Dwarf

In this study we have investigated the effect on the bioactivity of pituitary-derived human growth hormone (hGH) and recombinant bovine (b) GH after the addition of various concentrations of the water soluble cross-linking agent 1-ethyl-3(3-dimethylaminopropyl) carbodiimide (EDC; 6.25-100 mg/ml). The biological activity of resulting cross-linked reactions were determined by its ability to promote incorporation of 35SO4(2-) into costal cartilage of hypopituitary Snell dwarf mice in vivo. Administration of EDC-treated hGH solutions resulted in a significant enhancement of hormone activity in vivo compared with non-cross-linked samples. A similar significant enhancement of bGH activity in vivo was also observed when solutions containing recombinant bGH were cross-linked using EDC. For both hGH and bGH the degree of enhancement appears to be dose-dependent for the concentration of EDC (6.25-100 mg/ml for hGH; 6.25-50 mg/ml for bGH) present in the cross-linking reactions. SDS-PAGE analysis of EDC cross-linked solutions containing hGH and bGH spiked with 125I-hGH and 125I-bGH respectively revealed that dimeric GH was the primary cross-linked component. Increasing the concentration of EDC in cross-linking reactions resulted in increased formation of dimeric hGH and bGH. There was a significant correlation between the amount of GH dimer present and the increase in biological activity, suggesting that GH dimers were responsible for the enhanced biological activity. This was confirmed by the enhanced biological activity of a purified preparation of EDC cross-linked dimeric hGH. In conclusion, covalently cross-linked GH dimers reported here have enhanced bioactivity in vivo. However, since naturally occurring GH dimers are known to have reduced biological activity, this work suggests that the structure of EDC cross-linked GH dimers differs fundamentally from that of native dimeric hGH.

scholarly journals A Paradoxical Mutant GATA Factor

2004 ◽  
Vol 3 (2) ◽  
pp. 393-405 ◽  
Author(s):  
M. Isabel Muro-Pastor ◽  
Joseph Strauss ◽  
Ana Ramón ◽  
Claudio Scazzocchio
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Double Helix ◽  
Constitutive Expression ◽  
Nitrogen Sources ◽  
Loss Of Function ◽  
Gata Factor ◽  
Dna Double Helix

ABSTRACT The niiA (nitrite reductase) and niaD (nitrate reductase) genes of Aspergillus nidulans are subject to both induction by nitrate and repression by ammonium or glutamine. The intergenic region between these genes functions as a bidirectional promoter. In this region, nucleosomes are positioned under nonexpression conditions. On nitrate induction under derepressing conditions, total loss of positioning occurs. This is independent of transcription and of the NirA-specific transcription factor but absolutely dependent on the wide-domain GATA-binding AreA factor. We show here that a 3-amino-acid deletion in the basic carboxy-terminal sequence of the DNA-binding domain results in a protein with paradoxical properties. Its weak DNA binding is consistent with its loss-of-function phenotype on most nitrogen sources. However, it results in constitutive expression and superinducibility of niiA and niaD. Nucleosome loss of positioning is also constitutive. The mutation partially suppresses null mutations in the transcription factor NirA. AreA binds NirA in vitro, and the mutation does not affect this interaction. The in vivo methylation pattern of the promoter is drastically altered, suggesting the recruitment of one or more unknown transcription factors and/or a local distortion on the DNA double helix.

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