E. coli Rep helicase and RecA recombinase unwind G4 DNA and are important for resistance to G4-stabilizing ligands

Tapas Paul, Andrew F. Voter, Rachel R. Cueny, Momčilo Gavrilov, Taekjip Ha, James L. Keck, Sua Myong

Research output: Contribution to journalArticlepeer-review

Abstract

G-quadruplex (G4) DNA structures can form physical barriers within the genome that must be unwound to ensure cellular genomic integrity. Here, we report unanticipated roles for the Escherichia coli Rep helicase and RecA recombinase in tolerating toxicity induced by G4-stabilizing ligands in vivo. We demonstrate that Rep and Rep-X (an enhanced version of Rep) display G4 unwinding activities in vitro that are significantly higher than the closely related UvrD helicase. G4 unwinding mediated by Rep involves repetitive cycles of G4 unfolding and refolding fueled by ATP hydrolysis. Rep-X and Rep also dislodge G4-stabilizing ligands, in agreement with our in vivo G4-ligand sensitivity result. We further demonstrate that RecA filaments disrupt G4 structures and remove G4 ligands in vitro, consistent with its role in countering cellular toxicity of G4-stabilizing ligands. Together, our study reveals novel genome caretaking functions for Rep and RecA in resolving deleterious G4 structures.

Original languageEnglish (US)
Pages (from-to)6640-6653
Number of pages14
JournalNucleic acids research
Volume48
Issue number12
DOIs
StatePublished - Jul 9 2020

ASJC Scopus subject areas

  • Genetics

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