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DNA Topoisomerases

DNA Topoisomerases

Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...

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Updated: Jun 24, 2025

Iterative Optimization of DNA Duplexes for Crystallization of SeqA-DNA Complexes

Iterative Optimization of DNA Duplexes for Crystallization of SeqA-DNA Complexes

Published on: November 1, 2012

Structural Optimization of Azacryptands for Targeting Three-Way DNA Junctions.

Angélique Pipier¹, Titouan Chetot², Apollonia Kalamatianou²

¹Institut de Chimie Moléculaire, ICMUB CNRS UMR6302, 9, Avenue Alain Savary, 21078, Dijon, France.

Angewandte Chemie (International Ed. in English)

|June 14, 2024

Summary

Researchers identified novel azacryptands, TrisNP-amphi and TrisNP-ana, as high-affinity, selective ligands for three-way DNA junctions (TWJs). These molecules offer new tools for cancer therapy and understanding TWJ roles in genomic stability.

Keywords:

DNA junctions NMR in vitro assays ligands molecular dynamics

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Published on: September 21, 2017

Area of Science:

Molecular Biology
Medicinal Chemistry
Genomics

Background:

Non-B-DNA structures like G-quadruplexes and DNA junctions form during DNA transactions.
These structures can impede DNA polymerase, causing DNA damage and genomic instability.
Stabilizing noncanonical DNA structures is a potential anticancer strategy targeting rapidly dividing cancer cells.

Purpose of the Study:

To identify high-affinity and selective ligands for three-way DNA junctions (TWJs).
To explore the potential of TWJ ligands in anticancer therapies.
To develop molecular tools for investigating the cellular roles of TWJs.

Main Methods:

In vitro techniques including competitive FRET-melting and TWJ Screen assays for affinity and selectivity.
Functional tests such as qPCR and Taq stop assays.
Structural analyses using molecular dynamics and NMR investigations.

Main Results:

Novel azacryptands, TrisNP-amphi and TrisNP-ana, were identified as promising TWJ ligands.
These ligands exhibit high affinity and selectivity for TWJs.
The identified ligands can serve as molecular tools for further research.

Conclusions:

TrisNP-amphi and TrisNP-ana are the first recognized reference ligands for TWJs with high affinity and selectivity.
These ligands can be utilized to investigate the cellular functions of TWJs.
Exploiting TWJ-ligand interactions presents a novel avenue for anticancer drug development.