E. coli Rep helicase and RecA recombinase unwind G4 DNA and are important for resistance to G4-stabilizing ligands-Reference-Cited by-同舟云学术

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

Published:2020-05-25 Issue:12 Volume:48 Page:6640-6653
ISSN:0305-1048
Container-title:Nucleic Acids Research
language:en
Short-container-title:

Author:

Paul Tapas¹,Voter Andrew F²,Cueny Rachel R²,Gavrilov Momčilo¹,Ha Taekjip¹³⁴,Keck James L²^ORCID,Myong Sua¹³^ORCID

Affiliation:

1. Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA

2. Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA

3. Physics Frontier Center (Center for Physics of Living Cells), University of Illinois, 1110 W. Green St., Urbana, IL 61801, USA

4. Howard Hughes Medical Institute, Johns Hopkins University, USA

Abstract

AbstractG-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.

Funder

National Institutes of Health

National Science Foundation Physics Frontiers Center Program

Center for the Physics of Living Cells

Publisher

Oxford University Press (OUP)

Subject

Genetics

Link

http://academic.oup.com/nar/article-pdf/48/12/6640/33468744/gkaa442.pdf

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