Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

A guanine-flipping and sequestration mechanism for G-quadruplex unwinding by RecQ helicases

Journal Article · · Nature Communications
 [1];  [2];  [2];  [2];  [3]
  1. Univ. of Wisconsin School of Medicine and Public Health, Madison, WI (United States); DOE/OSTI
  2. Johns Hopkins Univ., Baltimore, MD (United States)
  3. Univ. of Wisconsin School of Medicine and Public Health, Madison, WI (United States)
Homeostatic regulation of G-quadruplexes (G4s), four-stranded structures that can form in guanine-rich nucleic acids, requires G4 unwinding helicases. The mechanisms that mediate G4 unwinding remain unknown. We report the structure of a bacterial RecQ DNA helicase bound to resolved G4 DNA. Unexpectedly, a guanine base from the unwound G4 is sequestered within a guanine-specific binding pocket. Disruption of the pocket in RecQ blocks G4 unwinding, but not G4 binding or duplex DNA unwinding, indicating its essential role in structure-specific G4 resolution. A novel guanine-flipping and sequestration model that may be applicable to other G4-resolving helicases emerges from these studies.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
NIH; USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1478097
Journal Information:
Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 9; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

References (45)

Hhal methyltransferase flips its target base out of the DNA helix journal January 1994
On base flipping journal July 1995
UvrD Helicase Unwinds DNA One Base Pair at a Time by a Two-Part Power Stroke journal December 2006
DNA Replication through G-Quadruplex Motifs Is Promoted by the Saccharomyces cerevisiae Pif1 DNA Helicase journal May 2011
A Conserved G4 DNA Binding Domain in RecQ Family Helicases journal May 2006
RecQ helicases in DNA double strand break repair and telomere maintenance journal August 2012
A nucleotide-flipping mechanism from the structure of human uracil–DNA glycosylase bound to DNA journal November 1996
G quadruplexes are genomewide targets of transcriptional helicases XPB and XPD journal March 2014
Essential role of limiting telomeres in the pathogenesis of Werner syndrome journal July 2004
The DNA helicase BRIP1 is defective in Fanconi anemia complementation group J journal August 2005
DNA secondary structures: stability and function of G-quadruplex structures journal October 2012
Intramolecular folding in three tandem guanine repeats of human telomeric DNA journal January 2012
Single-molecule imaging reveals a common mechanism shared by G-quadruplex–resolving helicases journal July 2016
Shuttling along DNA and directed processing of D-loops by RecQ helicase support quality control of homologous recombination journal January 2017
The Bloom’s Syndrome Helicase Unwinds G4 DNA journal October 1998
Human Werner Syndrome DNA Helicase Unwinds Tetrahelical Structures of the Fragile X Syndrome Repeat Sequence d(CGG) n journal April 1999
Crystal structures of open and closed forms of binary and ternary complexes of the large fragment of Thermus aquaticus DNA polymerase I: structural basis for nucleotide incorporation journal December 1998
High-resolution structure of the E.coli RecQ helicase catalytic core journal October 2003
The Saccharomyces cerevisiae Sgs1 helicase efficiently unwinds G-G paired DNAs journal May 1999
Substrate-specific inhibition of RecQ helicase journal April 2001
Genomic distribution and functional analyses of potential G-quadruplex-forming sequences in Saccharomyces cerevisiae journal November 2007
Bloom Syndrome: A Mendelian Prototype of Somatic Mutational Disease journal January 1993
Phaser crystallographic software journal July 2007
Neisseria gonorrhoeae RecQ Helicase HRDC Domains Are Essential for Efficient Binding and Unwinding of the pilE Guanine Quartet Structure Required for Pilin Antigenic Variation journal March 2013
Human RecQ Helicases in DNA Repair, Recombination, and Replication journal June 2014
Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36. text January 2018
PHENIX: a comprehensive Python-based system for macromolecular structure solution. text January 2010
Conferring Substrate Specificity to DNA Helicases: Role of the RecQ HRDC Domain journal August 2005
RecA-Binding pilE G4 Sequence Essential for Pilin Antigenic Variation Forms Monomeric and 5′ End-Stacked Dimeric Parallel G-Quadruplexes journal December 2012
An RNA G-quadruplex in the 5′ UTR of the NRAS proto-oncogene modulates translation journal February 2007
Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36 journal June 2018
Structural mechanisms of DNA binding and unwinding in bacterial RecQ helicases journal March 2015
Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription journal August 2002
Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD (ERCC2) repair/transcription gene journal August 1997
The Role of Base Flipping in Damage Recognition and Catalysis by T4 Endonuclease V journal October 1997
The DEXH Protein Product of the DHX36 Gene Is the Major Source of Tetramolecular Quadruplex G4-DNA Resolving Activity in HeLa Cell Lysates journal September 2005
Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes journal April 2015
Genome-wide prediction of G4 DNA as regulatory motifs: Role in Escherichia coli global regulation journal May 2006
Phaser crystallographic software journal July 2007
Coot model-building tools for molecular graphics journal November 2004
Integration, scaling, space-group assignment and post-refinement journal January 2010
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
An Alternative DNA Structure Is Necessary for Pilin Antigenic Variation in Neisseria gonorrhoeae journal August 2009
Neisseria gonorrhoeae RecQ Helicase HRDC Domains Are Essential for Efficient Binding and Unwinding of the pilE Guanine Quartet Structure Required for Pilin Antigenic Variation journal March 2013
FANCJ Helicase Defective in Fanconia Anemia and Breast Cancer Unwinds G-Quadruplex DNA To Defend Genomic Stability journal April 2008

Cited By (4)

RNA G-Quadruplex is Resolved by Repetitive and ATP Dependent Mechanism of DHX36 journal February 2019
Quantifying the impact of small molecule ligands on G-quadruplex stability against Bloom helicase journal September 2019
Replication of G Quadruplex DNA journal January 2019
Homology sensing via non-linear amplification of sequence-dependent pausing by RecQ helicase journal August 2019

Similar Records

Structural mechanisms of DNA binding and unwinding in bacterial RecQ helicases
Journal Article · Sun Mar 22 20:00:00 EDT 2015 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1182325

Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36
Journal Article · Tue Jun 12 20:00:00 EDT 2018 · Nature (London) · OSTI ID:1544820

Molecular insights into RNA and DNA helicase evolution from the determinants of specificity for a DEAD-box RNA helicase
Journal Article · Thu Dec 11 19:00:00 EST 2014 · eLife · OSTI ID:1628825