G-quadruplex recognition and remodeling by the FANCJ helicase

Colin G Wu; Maria Spies

doi:10.1093/nar/gkw574

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G-quadruplex recognition and remodeling by the FANCJ helicase

Journal article

Open access

Peer reviewed

G-quadruplex recognition and remodeling by the FANCJ helicase

Colin G Wu and Maria Spies

Nucleic acids research, Vol.44(18), pp.8742-8753

10/14/2016

DOI: 10.1093/nar/gkw574

PMCID: PMC5062972

PMID: 27342280

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Abstract

Guanine rich nucleic acid sequences can form G-quadruplex (G4) structures that interfere with DNA replication, repair and RNA transcription. The human FANCJ helicase contributes to maintaining genomic integrity by promoting DNA replication through G4-forming DNA regions. Here, we combined single-molecule and ensemble biochemical analysis to show that FANCJ possesses a G4-specific recognition site. Through this interaction, FANCJ targets G4-containing DNA where its helicase and G4-binding activities enable repeated rounds of stepwise G4-unfolding and refolding. In contrast to other G4-remodeling enzymes, FANCJ partially stabilizes the G-quadruplex. This would preserve the substrate for the REV1 translesion DNA synthesis polymerase to incorporate cytosine across from a replication-stalling G-quadruplex. The residues responsible for G-quadruplex recognition also participate in interaction with MLH1 mismatch-repair protein, suggesting that the FANCJ activity supporting replication and its participation in DNA interstrand crosslink repair and/or heteroduplex rejection are mutually exclusive. Our findings not only describe the mechanism by which FANCJ recognizes G-quadruplexes and mediates their stepwise unfolding, but also explain how FANCJ chooses between supporting DNA repair versus promoting DNA replication through G-rich sequences.

Cell Line

Basic-Leucine Zipper Transcription Factors - metabolism

DNA, Single-Stranded - metabolism

Humans

Models, Molecular

DNA - metabolism

Fanconi Anemia Complementation Group Proteins - chemistry

DNA, Single-Stranded - chemistry

Recombinant Fusion Proteins

DNA - chemistry

Fanconi Anemia Complementation Group Proteins - metabolism

Basic-Leucine Zipper Transcription Factors - chemistry

Models, Biological

Protein Binding

G-Quadruplexes

Protein Conformation

Details

Title: Subtitle: G-quadruplex recognition and remodeling by the FANCJ helicase
Creators: Colin G Wu - Department of Biochemistry, University of Iowa Carver College of Medicine, 51 Newton Rd., 4-532 BSB, Iowa City, IA 52242, USA
Maria Spies - Department of Biochemistry, University of Iowa Carver College of Medicine, 51 Newton Rd., 4-532 BSB, Iowa City, IA 52242, USA maria-spies@uiowa.edu
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.44(18), pp.8742-8753
DOI: 10.1093/nar/gkw574
PMID: 27342280
PMCID: PMC5062972
NLM abbreviation: Nucleic Acids Res
ISSN: 0305-1048
eISSN: 1362-4962
Publisher: England
Grant note: R01 GM108617 / NIGMS NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 10/14/2016
Academic Unit: Radiation Oncology; Biochemistry and Molecular Biology
Record Identifier: 9984024539402771

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