A new publication in Nucleic Acids Research
Teamwork makes the dream work! Our team has combined the expertise of Sébastien Britton (biology, IPBS Toulouse), Anton Granzhan (chemistry, Institut Curie, Orsay), Nicolas Chéron (theoretical chemistry, ENS Paris) and their students to design a study on a series of azacryptands that interact with both G-quadruplexes (G4s) and three-way DNA junctions (TWJs) in vitro. We show here that the cellular properties of this new class of dual TWJ-/G4-ligands are mostly governed by their interactions with TWJs. We notably studied their ability to trigger DNA damage, exploit this to define valuable chemically induced synthetic lethality strategy and decipher (part of) their mechanism of action. A thrilling chemical biology project, which also provides the first bona fide demonstration of the existence of TWJs in human cells, now fully described in Nucleic Acids Res. (IF = 16.9) Dual targeting of higher-order DNA structures by azacryptands induces DNA junction-mediated DNA damage in cancer cells.
Joanna Zell, Katerina Duskova, Leïla Chouh, Madeleine Bossaert, Nicolas Chéron, Anton Granzhan, Sébastien Britton, David Monchaud