Long-range interactions between DNA-bound ligands.

P Samuelson; K Jansen; M Kubista

doi:10.1002/jmr.300070313

Home/Archive/PubMed

PubMed · 7880549

Long-range interactions between DNA-bound ligands.

P Samuelson·K Jansen·M Kubista

View original source ↗Export metadata ↓

Abstract

We have studied the interaction of the A:T specific minor-groove binding ligand 4',6-diamidino-2-phenylindole (DAPI) with synthetic DNA oligomers containing specific binding sites in order to investigate possible long-range interactions between bound ligands. We find that DAPI binds cooperatively to the oligomers. The degree of cooperativity increases with increasing number of binding sites and decreases with the separation between them. This dependence is paralleled by changes in the induced circular dichroism spectrum of DAPI, which decreases in intensity at 335 nm and increases at 365 nm. These results are consistent with an allosteric interaction of DAPI with DNA, where bound ligands cooperatively alter the structure of the DNA molecule. This structural change seems possible to induce under various conditions, including physiological. One consequence of allosteric binding is that ligands bound at a distance from each other sense each other's presence and influence each others' properties. If some regulatory proteins induce the same conformational change as DAPI, novel mechanisms for controlling gene expression can be anticipated.

Explore related subjects

Adenine Allosteric Regulation Base Sequence Circular Dichroism DNA Fluorescence Indoles Ligands Molecular Sequence Data Molecular Structure Nucleic Acid Conformation Thermodynamics Thymine Titrimetry Journal Article Research Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

P Samuelson, K Jansen, M Kubista. 1994. Long-range interactions between DNA-bound ligands.. https://doi.org/10.1002/jmr.300070313

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

A distinct subclade of AlkB family demethylases in ciliates safeguards the positional fidelity of eukaryotic N6-methyladenine (6mA).

DNA N6-methyladenine (6mA) is a newly recognized transcription-associated epigenetic mark in eukaryotes. While its methylation pathway has been well established, the identity of eukaryotic 6mA demethylase(s) responsible for its removal and dynamic regulation has remained elusive. Here, we identify and characterize DMT3 (TtALKBH5), an AlkB family dioxygenase in Tetrahymena thermophila, as a 6mA demethylase in ciliates and potentially several other unicellular eukaryotes with abundant 6mA and a defined AMT1 methyltransferase (MTase) complex, supported by genetic and molecular evidence. DMT3 acts on both fully and hemimethylated ApT dinucleotides, an activity partially facilitated by a naturally occurring cysteine-to-serine substitution. Genome profiling shows that DMT3 is enriched at transcription start sites (TSSs) of 6mA-enriched genes, complementary to the occupancy pattern of the AMT1 complex, where it selectively removes spurious 6mA deposited by AMT1. Genetic disruption of DMT3-mediated demethylation, either by knockout or catalytic inactivation, leads to aberrant 6mA accumulation at TSS regions, transcriptional dysregulation, altered chromatin accessibility, and impaired initiation of sexual reproduction. Notably, simultaneous removal of DMT3 and AMT1 eliminates these defects, indicating that spurious TSS 6mA underlies transcriptional and developmental impairment.

Adenine↗

PubMed2026

Optimizations of Cas12a- and Cas12i-based adenine base editors for efficient precision editing in the plant genome.

A strategy coupling high-activity nucleases with dimeric TadA-8e optimizes plant Cas12-based adenine base editors, boosts editing efficiency, and provides precise editors for crop breeding and genomics research.

Adenine↗

PubMed1996

Glutamine- and phosphate-containing hypotonic storage media better maintain erythrocyte membrane physical properties.

We have shown that red blood cell (RBC) adenosine-5'-triphosphate (ATP) is better maintained and that there is less hemolysis and K+ leakage in hypotonic experimental additive solutions (EASs) containing glutamine and glutamine plus phosphate (Pi) than in the conventional additive solution Adsol during blood bank storage. The objective of this study was to determine if the beneficial effect produced in these media correlates with better preservation of RBC membrane properties including lipid content, phospholipid organization, aminophospholipid transport (flippase), and prothrombin converting activity. Aliquots of packed RBCs were stored in EASs containing adenine, glucose, sodium chloride, and mannitol, with 10 mmol/L glutamine (EAS 44) or with 10 mmol/L glutamine and 20 mmol/L Pi(EAS 45), or in Adsol. RBC membranes were studied after 0, 28, 42, and 84 days of storage, and vesicle membranes were studied after 84 days. RBC cholesterol and phospholipid content remained significantly greater (P < .01) in EASs than in Adsol. The degree of membrane vesiculation was more than 50% lower in EASs than in Adsol (P < .01). After 42 days of storage, the accessibility of phosphatidylethanolamine to phospholipases was approximately 1.5 times greater for Adsol and EAS 44 samples than for EAS 45 samples (43.5% v 28%). The rates of phosphatidylserine transport were 43% to 70% lower for stored cells but were not dependent on storage media. The amounts of bands 3 and 4.1 in the microvesicle membranes were not statistically different in any of the preparations. These results suggest that storage of RBCs in glutamine and Pi-medium better maintains ATP, lipid content, and phospholipid asymmetry and results in decreased vesiculation.

Adenine↗