Related Experiment Video
Updated: Jul 26, 2025
09:32
Stable DNA Motifs, 1D and 2D Nanostructures Constructed from Small Circular DNA Molecules
Published on: April 12, 2019
6.5K
Organometallic Pillarplexes That Bind DNA 4-Way Holliday Junctions and Forks
James S Craig, Larry Melidis, Hugo D Williams
1Department of Chemistry, University of Zürich, Winterthurerstr. 190, 8057 Zürich, Switzerland.
Journal of the American Chemical Society
|June 15, 2023
Summary
Metallo-supramolecular pillarplexes bind open DNA 4-way (Holliday) junctions, a novel interaction. These compounds show potential for modulating DNA structures and exhibit antiproliferative activity in human cells.
Area of Science:
- Organometallic Chemistry
- Supramolecular Chemistry
- Molecular Biology
Background:
- Holliday junctions are crucial for DNA processes like recombination and repair.
- These junctions exist in dynamic open (biologically active) and closed conformations.
- Metallo-supramolecular pillarplexes possess structures suitable for interacting with open DNA cavities.
Purpose of the Study:
- To investigate the binding of metallo-supramolecular pillarplexes with DNA 4-way (Holliday) junctions.
- To explore the potential of pillarplexes in modulating DNA junction structures.
- To assess the biological activity and cellular localization of pillarplexes.
Main Methods:
- Experimental studies combined with Molecular Dynamics (MD) simulations.
- Analysis of pillarplex interaction with 3-way and 4-way DNA junctions.
- Assessment of antiproliferative activity and nuclear localization in human cells.
Main Results:
- Gold (Au) pillarplexes selectively bind to the open conformation of DNA 4-way (Holliday) junctions.
- Pillarplexes can disrupt 3-way junctions and rearrange both 3-way and 4-way junctions into Y-shaped forks.
- Silver (Ag) pillarplexes exhibit similar binding but lower stability; pillarplexes reach the nucleus and show antiproliferative effects.
Conclusions:
- Pillarplexes offer a novel method for targeting and modulating open DNA 4-way junctions.
- This work expands the possibilities for designing bioactive junction binders in organometallic chemistry.
- Pillarplexes represent a promising new class of compounds for DNA nanostructures and potential therapeutics.
More Related Videos
Related Concept Videos
01:03Single-Strand DNA Binding Proteins
14.4K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
14.4K
02:04Fixing Double-strand Breaks
12.7K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
12.7K
02:37Restarting Stalled Replication Forks
5.8K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.8K
00:55DNA Helicases
21.6K
DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
21.6K
02:31Homologous Recombination
50.7K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
50.7K
01:02The DNA Replication Fork
36.2K
An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
36.2K