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Date publication

décembre 2025

Journal

Nature structural & molecular biology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr LAMOUR Valérie


Tous les auteurs :
Vidmar V, Borde C, Bruno L, Miropolskaya N, Takacs M, Batisse C, Saint-André C, Zhu C, Espéli O, Lamour V, Weixlbaumer A

Résumé

During transcription, RNA polymerase (RNAP) continuously unwinds and rewinds DNA, generating negative and positive supercoils upstream and downstream, respectively. Using single-particle cryo-EM, we elucidated how bacterial RNAP and DNA topoisomerase I (TopoI), which relaxes negative supercoils, operate in close spatial proximity. TopoI binds to relaxed DNA upstream of RNAP, and this involves a conformational switch in the TopoI functional domains. This suggests that TopoI exerts a sensing role before the formation of negative supercoils. On DNA substrates mimicking negatively supercoiled DNA, TopoI threads one strand into the active site for cleavage and binds the complementary strand with an auxiliary domain. Transcriptomic and phenotypic analyses suggest that mutations affecting conformational changes in TopoI impact gene expression and operon polarity in bacteria. In summary, we propose a comprehensive model for DNA relaxation in the proximity of active bacterial transcription.

Référence

Nat Struct Mol Biol. 2025 12 1;: