Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN

UniProt Q14191 Organism Homo sapiens Gene RECQ3, RECQL2, WRN EC 3.1.-.-, 5.6.2.4

Also known as: RECQ3, RECQL2, WRN

Function

Multifunctional enzyme that has magnesium and ATP-dependent 3'-5' DNA-helicase activity on partially duplex substrates. Also has 3'->5' exonuclease activity towards double-stranded (ds)DNA with a 5'-overhang. Has no nuclease activity towards single-stranded (ss)DNA or blunt-ended dsDNA. Helicase activity is most efficient with (d)ATP, but (d)CTP will substitute with reduced efficiency; strand displacement is enhanced by single-strand binding-protein (heterotrimeric replication protein A complex, RPA1, RPA2, RPA3). Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity). Plays a role in double-strand break repair after gamma-irradiation. Unwinds some G-quadruplex DNA (d(CGG)n tracts); unwinding seems to occur in both 5'-3' and 3'-5' direction and requires a short single-stranded tail. d(CGG)n tracts have a propensity to assemble into tetraplex structures; other G-rich substrates from a telomeric or IgG switch sequence are not unwound. Depletion leads to chromosomal breaks and genome instability.

Classification

Family (Pfam): PF00270 DEAD, PF01612 DNA_pol_A_exo1, PF00271 Helicase_C, PF00570 HRDC, PF14493 HTH_40, PF16124 RecQ_Zn_bind, PF09382 RQC
InterPro: 3'-5'_exonuclease_dom, DEAD/DEAH_box_helicase_dom, DNA_helicase_ATP-dep_RecQ, Helicase_ATP-bd, Helicase_C-like, Helicase_HTH, HRDC-like_sf, HRDC_dom, HRDC_dom_sf, P-loop_NTPase, RecQ_Zn-bd, RNaseH-like_sf, RNaseH_sf, RQC_domain, WH-like_DNA-bd_sf, WH_DNA-bd_sf
Functional cluster: Zinc-Finger Nucleic-Acid-Binding & Methyltransferases

Experimental structures · PDB · 40

2AXL NMR
2DGZ NMR
2E1E X-ray 2.30A
2E1F X-ray 2.00A
2FBT X-ray 2.05A
2FBV X-ray 2.40A
2FBX X-ray 2.20A
2FBY X-ray 2.00A
2FC0 X-ray 2.00A
3AAF X-ray 1.90A
6TYV X-ray 1.93A
6YHR X-ray 2.20A
… and 28 more

A predicted model is available from AlphaFold.

Gene Ontology · 51

Disease associations

colorectal cancer MONDO:0005575
Werner syndrome MONDO:0010196

Neighborhood · nearest proteins

Nearest neighbours of Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN 1 shared papers
ATP-dependent DNA helicase Q5 1 shared papers
ATP-dependent RNA helicase SUPV3L1, mitochondrial 1 shared papers
Exonuclease 1 1 shared papers
Putative ATP-dependent DNA helicase Q1 1 shared papers
ATP-dependent helicase wrn-1 1 shared papers
DNA repair protein Ku80 1 shared papers
Cell cycle regulator of non-homologous end joining 2 shared papers
ATP-dependent RNA helicase SUPV3L1, mitochondrial 1 shared papers
RecQ-like DNA helicase Blm 1 shared papers
DNA-dependent protein kinase catalytic subunit 1 shared papers
Protein PML 1 shared papers

Literature · 46 cited papers

Structure of the helicase core of Werner helicase, a key target in microsatellite instability cancers. Life. Sci Alliance · 2021
Ligand binding characteristics of the Ku80 von Willebrand domain. DNA Repair · 2020
Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins. Nat. Commun. · 2016
Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis. BMC Med. Genomics · 2013
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
RECQL5 plays co-operative and complementary roles with WRN syndrome helicase. Nucleic Acids Res. · 2013
N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
Promyelocytic leukemia protein interacts with werner syndrome helicase and regulates double-strand break repair in gamma-irradiation-induced DNA damage responses. Biochemistry (Mosc.) · 2011
System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
Structural basis for DNA strand separation by the unconventional winged-helix domain of RecQ helicase WRN. Structure · 2010
… and 34 more in the literature graph

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