Affinage

WRN

Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN · UniProt Q14191

Length
1432 aa
Mass
162.5 kDa
Annotated
2026-04-28
100 papers in source corpus 55 papers cited in narrative 55 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WRN is a RecQ-family DNA helicase/exonuclease that maintains genome integrity by resolving non-canonical DNA structures at replication forks, telomeres, and double-strand breaks, and by coordinating repair pathway choice. Its 3'→5' helicase unwinds Holliday junctions, D-loops, G-quadruplexes, and cruciform structures formed at expanded TA-dinucleotide repeats, while its DnaQ-family 3'→5' exonuclease processes DNA ends; RPA converts WRN's intrinsically repetitive unwinding into processive superhelicase activity, and WRN cooperates with DNA2 to mediate long-range 5'→3' end resection for homologous recombination (PMID:25122754, PMID:29668972, PMID:36541070). WRN additionally plays non-enzymatic scaffolding roles—stabilizing RAD51 at stalled forks, suppressing MRE11/CtIP-mediated alt-NHEJ, and promoting classical NHEJ—and its enzymatic activities are tuned by phosphorylation (ATR at S1141, ATM, CDK1 at S1133), acetylation (CBP/p300, reversed by SIRT1), and MDM2-mediated ubiquitin-dependent degradation (PMID:27634057, PMID:20428248, PMID:30532073, PMID:27922005). WRN helicase activity is selectively essential in microsatellite-instable cancers, where it prevents MUS81-mediated chromosome shattering at expanded TA-repeat cruciform structures, and allosteric small-molecule inhibitors recapitulate this synthetic lethality in vivo (PMID:30971823, PMID:32999459, PMID:38658754).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 High

    Establishing WRN as a dual-activity enzyme acting on recombination and replication intermediates: WRN was shown to possess intrinsic 3'→5' exonuclease activity on diverse substrates and to branch-migrate Holliday junctions, localizing with RPA at stalled replication forks—defining its biochemical repertoire beyond simple helicase function.

    Evidence In vitro exonuclease assays on dsDNA/RNA heteroduplexes; in vitro Holliday junction migration; immunofluorescence co-localization with RPA in HU-arrested cells

    PMID:10871373 PMID:11256630

    Open questions at the time
    • Physiological substrates in vivo not yet identified
    • Mechanism coupling helicase and exonuclease on same substrate unknown
    • Oligomerization state on DNA intermediates unclear
  2. 2002 High

    Defining WRN's preferred DNA structures and regulatory interactions: WRN was found to disrupt and degrade D-loops, interact with RAD52 at stalled forks (stimulating strand annealing), and function in the nucleolus to promote rRNA transcription via an RNA Pol I-associated complex—broadening its roles beyond canonical DSB repair.

    Evidence In vitro D-loop disruption/exonuclease assays; FRET co-localization of WRN-RAD52 in vivo; co-IP with RNA Pol I subunit; rRNA transcription rescue in WS fibroblasts

    PMID:11971179 PMID:12427008 PMID:12750383

    Open questions at the time
    • In vivo relevance of D-loop processing for recombination outcome unresolved
    • Mechanism of WRN stimulation of rRNA synthesis unclear
    • Whether nucleolar and repair functions are mutually exclusive unknown
  3. 2002 High

    Identifying p53 as a direct modulator of WRN helicase activity on recombination intermediates, and FEN-1 as a downstream effector stimulated by WRN for flap processing.

    Evidence In vitro p53 inhibition of WRN Holliday junction unwinding with phospho-site mapping; in vitro FEN-1 cleavage stimulation kinetics with purified WRN

    PMID:12080066 PMID:12356323

    Open questions at the time
    • In vivo significance of p53-WRN regulatory axis for recombination control not demonstrated
    • Whether WRN-FEN-1 cooperation occurs at Okazaki fragments in cells unconfirmed
  4. 2003 High

    Revealing that WRN has a non-catalytic scaffolding function in DSB repair: enzymatic-dead WRN mutants substantially complemented NHEJ defects in WS cells, establishing that WRN contributes to repair pathway organization independently of its helicase and exonuclease.

    Evidence Complementation of WRN−/− cells with helicase-dead, exonuclease-dead, and double-mutant WRN; NHEJ and HR assays

    PMID:12934712

    Open questions at the time
    • Identity of the structural interaction partners mediating scaffolding unknown
    • Relative contribution of enzymatic vs. structural roles at different lesion types unresolved
  5. 2005 High

    Establishing WRN's telomere-specific functions: POT1 and TRF2 directly stimulate WRN unwinding of telomeric substrates, and WRN helicase activity represses telomere-telomere recombination (T-SCE), preventing ALT pathway engagement.

    Evidence In vitro helicase stimulation by POT1 and TRF2 on telomeric substrates; T-SCE quantification by CO-FISH with WT vs. helicase-dead WRN reconstitution

    PMID:14712220 PMID:16030011 PMID:16264192

    Open questions at the time
    • Step-by-step mechanism of WRN at the t-loop not defined
    • Whether WRN loss is sufficient to trigger ALT in human cells unclear
  6. 2006 High

    Structural elucidation of the WRN exonuclease and HRDC domains: the exonuclease uses a two-metal-ion DnaQ-family mechanism stimulated by Ku70/80, while the HRDC domain is adapted for protein-protein interactions rather than DNA binding—providing a structural basis for WRN's multi-partner scaffolding.

    Evidence X-ray crystallography of exonuclease and HRDC domains; active-site mutagenesis; Ku70/80 stimulation assays; cell-based NHEJ assay

    PMID:16622405 PMID:17148451

    Open questions at the time
    • Full-length WRN structure unavailable
    • How Ku stimulation of exonuclease is mechanistically achieved at the structural level unknown
  7. 2008 High

    Defining WRN's post-translational regulation and its functional consequences: CBP/p300 acetylation modulates WRN enzymatic activities and stability (reversed by SIRT1), while WRN is required for ATM activation and the intra-S checkpoint after ICL damage and for normal replication fork progression after genotoxic stress.

    Evidence In vitro acetylation/deacetylation assays; helicase/exonuclease activity on acetylated WRN; SIRT1 co-IP; ATM pathway readouts after WRN KD; DNA fiber analysis of fork speed

    PMID:18203716 PMID:18250621 PMID:18398454 PMID:18596239

    Open questions at the time
    • Site-specific acetylation effects on individual activities not fully dissected
    • Whether acetylation-dependent WRN stabilization is the primary protective mechanism in DNA damage unclear
  8. 2008 High

    Single-molecule studies revealed WRN's intrinsic unwinding mechanism—repetitive reciprocating translocation on ssDNA—and showed that RPA converts WRN into a processive superhelicase, explaining how an inherently weak motor achieves kilobase-scale unwinding in vivo.

    Evidence Single-molecule FRET and magnetic tweezers on forked and G4-containing substrates; varying RPA concentrations

    PMID:28266653 PMID:29668972

    Open questions at the time
    • Whether other protein partners similarly convert WRN processivity unknown
    • In vivo processivity measurements lacking
  9. 2010 High

    Phosphorylation cascades controlling WRN at stalled and collapsed forks were mapped: ATR phosphorylation enables WRN focal accumulation and prevents DSBs at stalled forks, while ATM phosphorylation promotes RAD51-dependent fork recovery; acetylation-dependent stabilization protects WRN from ubiquitin-mediated degradation.

    Evidence In vitro kinase assays; phospho-mutant WRN alleles with immunofluorescence and fiber assays; acetylation site mass spectrometry; ubiquitination and stability assays

    PMID:20428248 PMID:20802463

    Open questions at the time
    • Hierarchy and temporal ordering of ATR vs. ATM phosphorylation events at individual forks unknown
    • Ubiquitin E3 ligase responsible for constitutive WRN turnover at this stage unidentified
  10. 2014 High

    WRN was placed in a defined end-resection pathway: WRN and DNA2 form a physical complex that, together with RPA, mediates 5'→3' long-range resection genetically distinct from BLM-dependent resection, while NBS1 recruits WRN to stabilize RAD51 and limit MRE11-dependent nascent strand degradation.

    Evidence In vitro resection reconstitution with purified WRN, DNA2, RPA; siRNA epistasis in human cells; DNA fiber analysis of nascent strand protection; NBS1 FHA domain mapping

    PMID:25122754 PMID:25456133

    Open questions at the time
    • Structural basis for WRN-DNA2 cooperation not resolved
    • How WRN is handed off between resection and RAD51 loading unclear
  11. 2016 High

    CDK1 phosphorylation at S1133 was shown to license WRN for MRE11 complex interaction and DNA2-dependent resection at collapsed forks, determining the choice between HR and NHEJ; ATR phosphorylation at S1141 triggers WRN ubiquitination and controlled degradation enabling dynamic fork interactions; separately, WRN enzymatic and non-enzymatic activities were dissected for their distinct roles in promoting c-NHEJ versus suppressing alt-NHEJ.

    Evidence CDK1 kinase assay and phospho-mutant alleles with resection/HR assays; ATR-dependent ubiquitination and degradation assays; chromosome breakage with S1141A mutant; end-joining assays with enzymatic WRN mutants

    PMID:26695548 PMID:27634057 PMID:27922005

    Open questions at the time
    • Whether phosphorylation events are sequential or parallel at individual breaks unknown
    • E3 ligase mediating S1141-dependent ubiquitination not identified
  12. 2018 High

    MDM2 was identified as an E3 ubiquitin ligase for WRN, promoting WRN degradation after DNA damage and contributing to cellular senescence in a p53-independent manner—providing a direct link between WRN protein homeostasis and the aging phenotype.

    Evidence Co-IP; in vitro and in vivo ubiquitination assays; protein stability assays; senescence rescue by WRN overexpression

    PMID:30532073

    Open questions at the time
    • Whether MDM2 is the sole damage-induced E3 ligase for WRN unknown
    • Regulation of MDM2-WRN interaction not characterized
  13. 2019 High

    WRN helicase was identified as selectively essential in MSI cancers: loss of WRN helicase (but not exonuclease) causes DSBs and apoptosis specifically in MSI cells, validated in genetic screens, cell panels, and xenograft models—establishing WRN as a synthetic-lethal therapeutic target.

    Evidence CRISPR-Cas9 and RNAi screens across MSI/MSS cell panels; enzymatic-domain complementation; in vivo xenograft models

    PMID:30971823

    Open questions at the time
    • Molecular substrate explaining MSI selectivity not yet identified at this point
    • Biomarkers for patient stratification beyond MSI status not defined
  14. 2020 High

    The mechanistic basis of MSI-selective WRN essentiality was resolved: expanded TA-dinucleotide repeats in MSI cells form non-B DNA structures (cruciforms) that stall replication forks; WRN helicase unwinds these structures, and in its absence MUS81 cleaves them causing chromosome shattering.

    Evidence Genomic sequencing of repeat expansions; DNA fiber analysis; MUS81 depletion epistasis; chromosome fragility analysis

    PMID:32999459

    Open questions at the time
    • Whether other non-B DNA structures (G4, triplex) at repeats also contribute unknown
    • Threshold of repeat expansion length triggering WRN dependence undefined
  15. 2022 High

    WRN was shown to directly unfold cruciform DNA structures in vitro, preventing their cleavage by SLX1-SLX4, and to regulate SHOX transcription by resolving G-quadruplexes at the SHOX locus—demonstrating structure-specific unwinding as a unifying activity linking genome stability, transcriptional regulation, and skeletal development.

    Evidence In vitro cruciform resolution and SLX1-SLX4 protection assays; synergy with MutLα; wrn-null zebrafish skeletal phenotyping with SHOX rescue

    PMID:36114168 PMID:36541070

    Open questions at the time
    • Genome-wide catalog of WRN-dependent G4/cruciform loci lacking
    • Whether SHOX deregulation explains short stature in Werner syndrome patients untested
  16. 2024 High

    Two allosteric WRN helicase inhibitors (HRO761 and VVD-133214) were co-crystallized with WRN, defining the structural basis for pharmacological inhibition: both lock the D1-D2 helicase domain interface in an inactive conformation and recapitulate WRN genetic loss selectively in MSI tumors, validating WRN as a druggable target.

    Evidence X-ray crystallography of WRN-inhibitor complexes; biochemical helicase assays; chemoproteomics for covalent site identification; MSI-selective cellular and xenograft efficacy

    PMID:38658751 PMID:38658754

    Open questions at the time
    • Clinical efficacy and resistance mechanisms in patients unknown
    • Whether inhibitor-induced WRN degradation observed in MSI cells contributes to efficacy vs. catalytic inhibition alone unresolved
    • Long-term toxicity in normal tissues not characterized from mechanism studies

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length WRN structure showing how the exonuclease, helicase, RQC, HRDC, and annealing domains are spatially coordinated remains unavailable, and the in vivo dynamics of WRN switching between its enzymatic and scaffolding modes at individual replication forks or DSBs are undefined.
  • No full-length structure of WRN or WRN–DNA complex
  • In vivo single-molecule tracking of WRN at individual forks not achieved
  • Contribution of WRN's nucleolar rRNA function to the Werner syndrome aging phenotype untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 4 GO:0140657 ATP-dependent activity 4 GO:0016787 hydrolase activity 3 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 3 GO:0005730 nucleolus 2
Pathway
R-HSA-73894 DNA Repair 5 R-HSA-1643685 Disease 4 R-HSA-69306 DNA Replication 4 R-HSA-1640170 Cell Cycle 3 R-HSA-8953854 Metabolism of RNA 1
Partners
DNA2FEN1POT1RAD52RPA1TP53TRF2XRCC5
Complex memberships
WRN-DNA2-RPA resection complex

Evidence

Reading pass · 55 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 WRN promotes ATP-dependent translocation (branch migration) of Holliday junctions in vitro, and co-localizes with RPA at nuclear foci in S-phase-arrested cells, consistent with a role in dissociating recombination intermediates at stalled replication forks. In vitro Holliday junction migration assay; immunofluorescence co-localization with RPA in hydroxyurea-arrested cells EMBO reports High 11256630
2000 WRN protein has intrinsic 3'→5' exonuclease activity that efficiently degrades 3' recessed strands of dsDNA or DNA-RNA heteroduplexes, removes mismatched 3' terminal nucleotides, and can initiate degradation from nicks or gaps; WRN also forms trimers and interacts with PCNA in vitro. In vitro exonuclease assays with purified human and mouse WRN; gel filtration for oligomerization; in vitro pulldown with PCNA Nucleic acids research High 10871373
2006 Crystal structures of the WRN exonuclease domain reveal a two-metal-ion catalytic mechanism homologous to DnaQ-family replicative proofreading exonucleases; Ku70/80 specifically stimulates WRN exonuclease activity; structure-based active-site mutations that inactivate WRN-exo alter DNA end joining in human cells. X-ray crystallography; in vitro exonuclease assays with active-site mutants; co-stimulation assays with Ku70/80; cell-based NHEJ assay with mutant WRN Nature structural & molecular biology High 16622405
2006 Crystal structure of the WRN HRDC domain reveals an alpha-helical bundle with unique N- and C-terminal extensions that enlarge its surface relative to yeast Sgs1 and E. coli RecQ; the domain lacks DNA-binding activity in vitro, suggesting it is adapted for protein-protein interactions rather than direct DNA contact. X-ray crystallography; in vitro DNA-binding assays; protease resistance and thermal stability assays The Journal of biological chemistry High 17148451
2014 Crystal structure of the WRN RQC domain bound to DNA shows that a β-wing hairpin within the winged-helix motif acts as a structural element to unwind DNA at branch points; this mechanism is conserved with BLM. Crystal structure analysis and structural comparison; functional modeling with Holliday junction docking Frontiers in genetics Medium 25400656
2002 WRN helicase efficiently disrupts D-loop structures in vitro via its helicase activity, and the WRN 3'→5' exonuclease degrades the 3' end of the inserted strand of D-loops, identifying D-loops as preferred substrates for WRN. In vitro D-loop disruption and degradation assays with purified WRN protein Biochemistry High 12427008
2002 p53 binds directly to BLM and WRN helicases and inhibits their ability to unwind Holliday junctions in vitro; specific p53 C-terminal residues (aa 373-383) mediate this inhibition, and phosphorylation at Ser376 or Ser378 abrogates the inhibition. In vitro helicase assays with purified p53; co-immunoprecipitation; phospho-p53 functional assays The Journal of biological chemistry High 12080066
2003 WRN plays both enzymatic and structural (non-enzymatic) roles in DNA DSB repair: both helicase-defective and exonuclease-defective WRN partially complement NHEJ defects in WS cells, the double enzymatic mutant complements nearly as well as wild-type WRN, indicating a structural scaffolding function independent of catalytic activities. Complementation of WRN-/- cells with enzymatic mutants (E-, H-, E-H-); NHEJ and HR assays Aging cell High 12934712
2003 WRN physically interacts with RAD52 in vivo (FRET co-localization at stalled replication fork foci); RAD52 modulates WRN helicase activity in a DNA-structure-dependent manner, and WRN stimulates RAD52-mediated strand annealing, suggesting coordinated roles in replication fork rescue. FRET in living cells; co-immunoprecipitation; in vitro helicase and strand-annealing assays The Journal of biological chemistry High 12750383
2004 TRF2 directly binds WRN in the absence of DNA and also binds telomeric-repeat-containing DNA substrates, facilitating their degradation specifically by WRN exonuclease, suggesting TRF2 recruits WRN for telomeric DNA processing in vivo. In vitro co-immunoprecipitation; in vitro exonuclease assays on telomeric substrates with and without TRF2 Oncogene High 14712220
2005 POT1 directly binds WRN and BLM and strongly stimulates their unwinding of long telomeric forked duplexes and D-loops in a telomeric-sequence-dependent manner; POT1 co-precipitates more WRN than BLM from nuclear extracts. In vitro helicase stimulation assays on telomeric substrates; GST pulldown of purified proteins; co-immunoprecipitation from HeLa nuclear extract The Journal of biological chemistry High 16030011
2002 WRN is a component of an RNA polymerase I-associated complex in the nucleolus, co-immunoprecipitating with the RPA40 subunit of RNA Pol I; WS fibroblasts have decreased rRNA transcription that is restored by wild-type WRN but not by a nucleolus-targeting mutant, indicating WRN promotes rRNA synthesis in the nucleolus. Co-immunoprecipitation with RNA Pol I subunit; rRNA transcription measurement in WS vs. WT fibroblasts; rescue with WT and mutant WRN Oncogene High 11971179
2008 SIRT1 interacts with WRN both in vitro and in vivo; WRN is acetylated by CBP/p300 acetyltransferase, which decreases its helicase and exonuclease activities and alters its nuclear distribution; SIRT1 deacetylates WRN and reverses these effects; DNA damage enhances the SIRT1-WRN interaction and SIRT1 is required for WRN translocation from nucleoplasm to nucleoli after damage. Co-immunoprecipitation in vitro and in vivo; in vitro deacetylation/acetylation assays; in vitro helicase and exonuclease assays on acetylated WRN; immunofluorescence localization The Journal of biological chemistry High 18203716
2010 WRN is directly phosphorylated by ATR at multiple C-terminal S/TQ residues following replication arrest; ATR-mediated phosphorylation is required for WRN accumulation in nuclear foci and co-localization with RPA, and prevents DSB formation at stalled forks. Separately, ATM phosphorylation of WRN is required for subsequent RAD51 recruitment and replication fork recovery after fork collapse. In vitro kinase assays with ATR/ATM; phospho-specific mutant alleles expressed in cells; immunofluorescence foci analysis; fiber assays for fork progression The EMBO journal High 20802463
2016 CDK1 phosphorylates WRN at S1133 at collapsed replication forks; this phosphorylation promotes interaction of WRN with the MRE11 complex and is essential for DNA2-dependent long-range DNA end resection and homologous recombination at replication-related DSBs, while loss of this phosphorylation licenses NHEJ. In vitro CDK1 kinase assay; phospho-mutant WRN alleles in cells; co-immunoprecipitation; resection and HR assays; immunofluorescence foci analysis Nature communications High 27634057
2010 CBP/p300 are the primary acetyltransferases for WRN; acetylation of six specific lysine residues stabilizes WRN by reducing its ubiquitination; SIRT1 deacetylates WRN and reverses this stabilization; WRN is strongly acetylated and stabilized following mitomycin C treatment, and cells expressing non-acetylatable WRN (6KR mutant) are hypersensitive to MMC. Identification of acetylation sites by mass spectrometry and mutagenesis; ubiquitination assays; pulse-chase protein stability assays; drug sensitivity assays with WRN-6KR cells PloS one High 20428248
2016 ATR-mediated phosphorylation of WRN at S1141 in response to replication stress leads to ubiquitination and controlled degradation of WRN, facilitating its reversible interaction with perturbed replication forks and enabling suppression of new origin firing and Rad51-dependent DSB repair; a phospho-resistant S1141 mutant causes chromosome breakage. In vivo phosphorylation assays; phospho-mutant WRN alleles; ubiquitination assays; DNA fiber analysis; chromosome breakage assays Oncotarget High 26695548
2018 MDM2 acts as an E3 ubiquitin ligase for WRN: MDM2 interacts with WRN in vivo and in vitro, induces WRN ubiquitination, and promotes WRN degradation following DNA damage; MDM2-dependent WRN degradation contributes to cellular senescence in a p53-independent manner. Co-immunoprecipitation in vivo and in vitro; ubiquitination assays; protein stability assays; senescence assays with WRN ectopic expression rescue Oncogene High 30532073
2008 p300-mediated acetylation of WRN stimulates its helicase and exonuclease activities in vitro and in vivo; acetylated WRN enhances DNA pol β-mediated strand displacement synthesis more than unacetylated WRN; long-patch BER is stimulated by histone deacetylase inhibition in WT but not WRN-depleted cells, implicating acetylated WRN in long-patch BER. In vitro acetylation followed by helicase/exonuclease assays; strand displacement synthesis assays; sodium butyrate treatment with BER measurement in WT vs. WRN-depleted cells PloS one High 18398454
2014 WRN and DNA2 physically interact and coordinate their enzymatic activities to mediate 5'→3' long-range DNA end resection in a reaction dependent on RPA; genetic epistasis in human cells shows WRN acts in the same resection pathway as DNA2 (WRN/DNA2 pathway), distinct from the BLM-TOPOIII α-RMI1-RMI2-mediated pathway. Co-immunoprecipitation; in vitro resection assays with purified WRN, DNA2, and RPA; siRNA epistasis in human cells with DSB resection measurement The Journal of biological chemistry High 25122754
2014 WRN has a non-enzymatic role in preserving nascent DNA strands after replication stress: the NBS1 FHA domain recruits WRN to replication-associated DSBs where WRN stabilizes Rad51 and limits MRE11 exonuclease activity; in the absence of WRN, MRE11 degrades newly replicated DNA. DNA fiber analysis of nascent strand length; co-immunoprecipitation; MRE11 inhibitor rescue; Rad51 foci analysis; NBS1 FHA domain interaction mapping Cell reports High 25456133
2016 WRN regulates the choice between classical NHEJ and alternative NHEJ (alt-NHEJ) at DSBs: WRN promotes c-NHEJ via helicase and exonuclease activities, while inhibiting alt-NHEJ through non-enzymatic functions by suppressing MRE11/CtIP recruitment and protecting DSB ends from 5' resection; loss of WRN combined with TRF2 loss increases telomere fusions dependent on CtIP. End-joining assays with enzymatic WRN mutants; co-immunoprecipitation; ChIP at DSBs; resection assays; double-KD epistasis in MEFs Nature communications High 27922005
2004 APE1 inhibits WRN helicase activity on BER single-strand break intermediates, likely by occluding the substrate; this inhibition is relieved by DNA polymerase β, suggesting a pol β-mediated handoff mechanism for WRN recruitment at BER intermediates. In vitro helicase assays on BER intermediates with APE1 and pol β; protein interaction studies The Journal of biological chemistry High 15385537
2002 WRN directly interacts with FEN-1 and stimulates FEN-1 cleavage efficiency (not DNA binding) on 5' flap substrates relevant to Okazaki fragment processing; the WRN-stimulatory mechanism is distinct from the PCNA-FEN-1 mechanism. In vitro FEN-1 cleavage kinetic assays with purified WRN; streptavidin-blocked substrate assays; interaction pulldown Biochemistry High 12356323
2005 WRN and BLM both bind the C-terminal 18 amino acid tail of FEN-1 adjacent to its PCNA-binding site; WRN facilitates FEN-1 binding to double-flap substrates through this protein-protein interaction; PCNA and WRN can act coordinately on FEN-1. Deletion mapping with truncated FEN-1 constructs; in vitro FEN-1 cleavage stimulation assays; interaction pulldowns Nucleic acids research High 16326861
2005 p53 directly binds WRN and RPA with low-nanomolar affinity; p53 inhibits RPA-stimulated WRN helicase activity on long M13 partial duplexes and on short forked duplexes independently of RPA; this inhibition is dependent on the WRN-p53 interaction site and is not seen with RECQ1. In vitro co-immunoprecipitation; in vitro helicase assays with purified proteins; affinity measurements; competitor DNA controls Cancer research High 15735006
2008 WRN helicase activity (measured by single-molecule FRET) is intrinsically weak and repetitive (unwinding only ~tens of bp), but binding of multiple RPA molecules converts WRN into a processive 'superhelicase' capable of unidirectionally unwinding >1 kb of dsDNA. Single-molecule FRET; magnetic tweezers; in vitro helicase assays with varying RPA concentrations Nucleic acids research High 29668972
2017 Single-molecule FRET analysis of WRN helicase reveals that its repetitive DNA unwinding is caused by reciprocating (back-and-forth) translocation of WRN along the same ssDNA strand, rather than complete dissociation/rebinding or strand switching. Single-molecule FRET (smFRET) with various DNA substrates including forked, overhanging, and G-quadruplex-containing DNAs Scientific reports High 28266653
2008 WRN's ssDNA annealing activity is mapped to a C-terminal 79 amino acid region (aa 1072-1150) between the RQC and HRDC domains; deletion of this region reduces/eliminates annealing activity, and the activity correlates with DNA binding and oligomerization of WRN. Truncation mapping with purified WRN fragments; in vitro ssDNA annealing assays; DNA binding and oligomerization assays Biochemistry High 18771289
2010 DNA-PKcs selectively stimulates WRN helicase (but not exonuclease) activity in vitro; DNA-PKcs knockdown cells have shortened telomeric G-tails, and this phenotype is rescued by WRN helicase overexpression, suggesting WRN and DNA-PKcs cooperate to maintain telomeric D-loops and G-tail length. In vitro helicase and exonuclease assays with DNA-PKcs; telomeric G-tail assays in DNA-PKcs knockdown cells; rescue with WRN overexpression Aging High 20519774
2011 XPG directly interacts with WRN, co-localizing in mid-to-late S-phase nuclear foci; the C-terminal domain of XPG stimulates WRN helicase activity; XPG has intrinsic strand annealing activity requiring its unstructured R- and C-terminal domains; XPG annealing is cooperative (not additive) with WRN annealing. Co-immunoprecipitation; domain mapping pulldowns; immunofluorescence co-localization; in vitro helicase stimulation assay; in vitro strand annealing assays Cell cycle High 21558802
2008 WRN is required for ATM activation and the intra-S checkpoint in response to interstrand cross-link-induced DSBs: siRNA depletion of WRN impairs ATM kinase activation and phosphorylation of downstream ATM targets, causes S-phase checkpoint defects, and leads to elevated γH2AX following psoralen cross-links. WRN siRNA knockdown; ATM kinase activity and substrate phosphorylation Western blots; S-phase checkpoint analysis; γH2AX foci quantification Molecular biology of the cell High 18596239
2008 WRN depletion markedly impairs replication fork elongation speed after MMS or hydroxyurea treatment (measured by DNA fiber/replication track analysis), establishing WRN as required for normal replication fork progression after DNA damage or arrest. Replication track analysis (DNA fiber stretching and fluorescence labeling); cell cycle kinetics analysis after WRN depletion Cell cycle High 18250621
2011 WRN inhibition by small molecule NSC 19630 (a maleimide that selectively inhibits WRN helicase but not BLM, FANCJ, RECQ1, RecQ, UvrD, or DnaB) induces apoptosis in a WRN-dependent manner, delayed S-phase progression, γH2AX and PCNA foci, and sensitizes cancer cells to PARP inhibitors and G4-binding compounds. In vitro helicase inhibition screen; selectivity profiling against other helicases; WRN-depleted and WRN-expressing cell comparisons; flow cytometry; γH2AX/PCNA foci PNAS High 21220316
2019 WRN helicase activity (but not exonuclease activity) is selectively essential in MSI cancer models: WRN depletion induces double-stranded DNA breaks, apoptosis, and cell cycle arrest selectively in MSI cells; MSI-selective dependence was confirmed in vivo in xenograft models. CRISPR-Cas9 KO and RNAi in cancer cell panels; in vitro and in vivo MSI model growth; complementation with helicase-dead vs. exonuclease-dead WRN mutants; γH2AX/apoptosis readouts Nature High 30971823
2020 Expanded TA-dinucleotide repeats in MSI cells form non-B DNA secondary structures that stall replication forks and require WRN helicase for unwinding; in the absence of WRN, these structures are cleaved by MUS81 nuclease leading to massive chromosome shattering. Genomic sequencing of repeat expansions; DNA fiber analysis; ATR checkpoint activation assays; MUS81 depletion epistasis; chromosome fragility analysis Nature High 32999459
2022 WRN helicase can directly unfold cruciform DNA structures in vitro, preventing their cleavage by SLX1-SLX4 endonuclease; TA-dinucleotide repeats are particularly prone to cruciform formation; mismatch repair complexes MutSα, MutSβ, and MutLα also reduce cruciform levels by a different mechanism, and WRN + MutLα show synergistic cruciform dissolution. In vitro cruciform resolution biochemical assays; SLX1-SLX4 protection assays; cell-free MMR complex assays; combined WRN+MutLα reconstitution The EMBO journal High 36541070
2024 HRO761 is a potent, allosteric WRN helicase inhibitor that binds at the interface of the D1 and D2 helicase domains, locking WRN in an inactive conformation; pharmacological inhibition recapitulates WRN genetic suppression phenotype, induces WRN degradation in MSI but not MSS cells, and causes tumor regression in MSI xenograft models. X-ray crystallography of WRN-HRO761 complex; biochemical helicase assays; selectivity profiling; cellular γH2AX and growth assays; MSI xenograft models Nature High 38658754
2024 VVD-133214 is a covalent allosteric WRN inhibitor that engages C727 in the helicase domain region subject to interdomain movement; it binds cooperatively with nucleotide and stabilizes compact conformations lacking the dynamic flexibility needed for helicase function, causing DSBs and cell death selectively in MSI-H cells. Chemoproteomics (cysteine-reactive probe profiling); covalent modification confirmed by mass spectrometry; helicase conformational analysis; cellular DSB and viability assays; in vivo xenograft models Nature High 38658751
2014 TRF2 stimulates WRN-mediated strand exchange specifically between telomeric substrates through interactions with both WRN and telomeric DNA, with TRF2's basic domain being particularly important; TRF1 does not stimulate WRN strand exchange; TRF2 is displaced from telomeric DNA by WRN independently of its ATPase/helicase activities. In vitro strand exchange assays on telomeric vs. non-telomeric substrates; domain-truncated TRF2 variants; EMSA Nucleic acids research High 24880691
2005 WRN helicase deficiency with telomerase co-deficiency elevates telomere sister chromatid exchange (T-SCE); reconstitution with wild-type WRN but not helicase-defective WRN suppresses T-SCEs, directly demonstrating that WRN helicase activity normally represses telomere-telomere recombination and prevents ALT pathway engagement. T-SCE assay by CO-FISH; WRN reconstitution with WT vs. helicase-dead mutant; telomere FISH; tumor analysis Genes & development High 16264192
2008 WRN controls telomeric-loop homologous recombination required for TRF2ΔB-mediated telomere shortening, and represses formation of spontaneous extrachromosomal telomeric circles (t-circles); both WRN exonuclease and helicase activities are required to suppress t-circle formation. T-circle detection in WS fibroblasts; reconstitution with WT and enzymatic WRN mutants; XRCC3 epistasis; telomere FISH Molecular and cellular biology High 18212065
2010 BCR/ABL forms a complex with WRN, causing WRN tyrosine phosphorylation and stimulation of its helicase and exonuclease activities; BCR/ABL also increases WRN expression via c-MYC-mediated transcription and Bcl-xL-dependent inhibition of caspase cleavage of WRN. Co-immunoprecipitation; in vitro helicase/exonuclease assays on BCR/ABL-stimulated WRN; WRN expression analysis; mRNA analysis Cancer research High 21123451
2016 HERC2 (a HECT E3 ligase) interacts with WRN, BLM, and RPA complexes during S-phase and facilitates RPA release onto ssDNA; HERC2 ubiquitinates RPA2, which is required for proper functioning of WRN/BLM complexes to suppress G-quadruplex DNA formation; HERC2 has an epistatic relationship with WRN and BLM in G4 suppression. Co-immunoprecipitation; CRISPR/Cas9 deletion of HERC2 catalytic domain; in vitro RPA-ssDNA loading assays; G4 foci quantification; epistasis by triple depletion Cancer research High 30279242
2011 WRN regulates the ATR-CHK1-mediated S-phase checkpoint in response to topoisomerase I inhibitor camptothecin: WRN depletion abolishes ssDNA accumulation, CHK1 phosphorylation, and CHK1 chromatin release in CPT-treated cells, but not in hydroxyurea-treated cells. WRN shRNA knockdown; CHK1 phosphorylation and chromatin fractionation assays; BrdU-ssDNA assay; replication fork elongation Journal of cell science High 22159421
2010 WRN participates in the translesion synthesis pathway in an ATM/NBS1-dependent manner: NBS1 FHA domain physically interacts with WRN and recruits it to DNA damage foci; DNA damage induces dissociation of WRN from PCNA, allowing PCNA ubiquitination required for TLS; loss of WRN causes constitutive PCNA ubiquitination and Rad18 interaction. Co-immunoprecipitation; immunofluorescence foci analysis; domain mapping of NBS1-WRN interaction; ubiquitinated PCNA western blots Mechanisms of ageing and development Medium 20600238
2016 RECQL5 physically interacts with WRN in vivo and in vitro, stimulates WRN helicase activity on stalled replication fork-like substrates, and is synthetically lethal with WRN; combined loss of RECQL5 and WRN severely compromises DNA replication. Co-immunoprecipitation; in vitro helicase stimulation assays; siRNA double depletion with cell viability and DNA replication fiber analysis; laser-induced DSB recruitment assays Nucleic acids research High 23180761
2016 Human DNA2 has a cryptic processive helicase activity that functionally integrates with WRN (or BLM) to form a heterodimeric molecular machine promoting dsDNA degradation; the DNA2 helicase motor promotes dsDNA degradation in conjunction with WRN to repair broken DNA. Bulk helicase assays; single-molecule assays; nuclease-dead DNA2 variant; in vitro reconstitution with WRN and DNA2 eLife High 27612385
2009 c-Myc overexpression accelerates S-phase and causes replication stress that requires WRN for repair: WRN depletion in c-Myc overexpressing cells increases DNA damage at sites of DNA synthesis and activates an ATR-CHK1-CHK2-p53 pathway leading to rapid senescence. BrdU labeling for S-phase progression; WRN siRNA depletion; γH2AX colocalization with BrdU; ATR/CHK1/CHK2/p53 pathway analysis; p53 depletion rescue PloS one High 19554081
2022 WRN and WRNIP1 are implicated in responding to R-loop-induced replication stress; WRN functions as a fork protection factor to prevent/remove pathological R-loops that cause genomic instability. Review of experimental findings including R-loop detection, fork progression assays in WRN-depleted cells International journal of molecular sciences Low 35163467
2022 WRN helicase is required for chondrogenesis and bone elongation; WRN helicase core regulates transcriptional expression of the short-stature homeobox gene SHOX by unwinding G-quadruplex structures in the SHOX locus; wrn-null zebrafish have impaired bone growth rescued by SHOX/shox overexpression. wrn-null zebrafish skeletal phenotyping; G-quadruplex unwinding assays at SHOX promoter; SHOX expression analysis; genetic rescue with SHOX overexpression in wrn-null zebrafish and WRN-null human cells Nature communications High 36114168
2008 WRN exonuclease is blocked by oxidatively induced base lesions (3' phosphates, phosphoglycolates, and others) and cannot excise these 3' obstructive termini; Ku70/80 can stimulate WRN exonuclease to bypass some but not all lesion types in the digested strand, while lesions in the non-digested strand also block WRN and cannot be overcome by Ku. In vitro exonuclease assays on substrates with specific oxidized bases; comparison with APE1, TREX1, and p53 exonucleases; Ku stimulation assays Nucleic acids research High 18658245
2016 WRN co-precipitates with HDAC1 and HDAC2; WRN and HDAC1 protect stalled replication forks additively: HDAC1 depletion exacerbates WRN-deficient fork reactivation defects, and the additive phenotype requires HDAC1 catalytic activity; RAD51 recruitment to stalled forks is reduced in WRN-depleted cells. Co-immunoprecipitation; siRNA epistasis screen; replication track analysis (ma-RTA); RAD51 foci analysis; HDAC catalytic mutant The Journal of biological chemistry Medium 27672210
2008 In a Drosophila ortholog study, DmWRNexo (encoded by CG7670) mutant flies show elevated mitotic DNA recombination (reciprocal exchange) and hypersensitivity to camptothecin, demonstrating that the WRN exonuclease domain has a conserved role in restraining illegitimate recombination and responding to topoisomerase I-induced damage. piggyBac insertional mutation of CG7670; somatic recombination frequency assay; CPT sensitivity assay; female sterility phenotyping Aging cell Medium 18346216
2007 CPT treatment induces WRN degradation via a ubiquitin-mediated proteasome pathway, and cells knockdown for WRN or treated with CPT show increased senescence; CPT-induced WRN degradation correlates with breast cancer cell sensitivity to CPT, while WRN remains stable in CPT-resistant cells. WRN protein stability assays with proteasome inhibitors; ubiquitination assays; senescence assays with β-galactosidase staining; WRN ectopic expression rescue; breast cancer cell line panel Oncotarget Medium 26959889

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 WRN helicase is a synthetic lethal target in microsatellite unstable cancers. Nature 340 30971823
2000 Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest. EMBO reports 329 11256630
2001 SGS1, the Saccharomyces cerevisiae homologue of BLM and WRN, suppresses genome instability and homeologous recombination. Nature genetics 283 11138010
2001 The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase. The EMBO journal 218 11179234
2014 DNA2 cooperates with the WRN and BLM RecQ helicases to mediate long-range DNA end resection in human cells. The Journal of biological chemistry 180 25122754
2006 The spectrum of WRN mutations in Werner syndrome patients. Human mutation 165 16673358
2011 Inhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress. Proceedings of the National Academy of Sciences of the United States of America 161 21220316
2005 POT1 stimulates RecQ helicases WRN and BLM to unwind telomeric DNA substrates. The Journal of biological chemistry 157 16030011
2020 Repeat expansions confer WRN dependence in microsatellite-unstable cancers. Nature 155 32999459
2005 Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway. Genes & development 154 16264192
2000 Mutations in the WRN gene in mice accelerate mortality in a p53-null background. Molecular and cellular biology 150 10757812
2008 Regulation of WRN protein cellular localization and enzymatic activities by SIRT1-mediated deacetylation. The Journal of biological chemistry 144 18203716
2010 ATR and ATM differently regulate WRN to prevent DSBs at stalled replication forks and promote replication fork recovery. The EMBO journal 138 20802463
2000 Characterization of the human and mouse WRN 3'-->5' exonuclease. Nucleic acids research 133 10871373
2006 WRN exonuclease structure and molecular mechanism imply an editing role in DNA end processing. Nature structural & molecular biology 130 16622405
2008 The RecQ helicase WRN is required for normal replication fork progression after DNA damage or replication fork arrest. Cell cycle (Georgetown, Tex.) 119 18250621
2003 WRN, the protein deficient in Werner syndrome, plays a critical structural role in optimizing DNA repair. Aging cell 118 12934712
2004 TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA. Oncogene 104 14712220
2003 WRN interacts physically and functionally with the recombination mediator protein RAD52. The Journal of biological chemistry 104 12750383
2002 The processing of Holliday junctions by BLM and WRN helicases is regulated by p53. The Journal of biological chemistry 104 12080066
2019 L-WRN conditioned medium for gastrointestinal epithelial stem cell culture shows replicable batch-to-batch activity levels across multiple research teams. Stem cell research 102 30933720
2016 WRN regulates pathway choice between classical and alternative non-homologous end joining. Nature communications 91 27922005
2002 The Werner syndrome helicase/exonuclease (WRN) disrupts and degrades D-loops in vitro. Biochemistry 90 12427008
2016 WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects. Human mutation 82 27667302
2024 Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers. Nature 79 38658754
2024 Chemoproteomic discovery of a covalent allosteric inhibitor of WRN helicase. Nature 76 38658751
2007 WRN at telomeres: implications for aging and cancer. Journal of cell science 75 17314245
2000 WRN helicase expression in Werner syndrome cell lines. Nucleic acids research 73 10606667
2004 Regulation of WRN helicase activity in human base excision repair. The Journal of biological chemistry 71 15385537
2009 c-Myc accelerates S-phase and requires WRN to avoid replication stress. PloS one 70 19554081
2002 WRN helicase accelerates the transcription of ribosomal RNA as a component of an RNA polymerase I-associated complex. Oncogene 70 11971179
2014 Nonenzymatic role for WRN in preserving nascent DNA strands after replication stress. Cell reports 66 25456133
2016 Human DNA2 possesses a cryptic DNA unwinding activity that functionally integrates with BLM or WRN helicases. eLife 65 27612385
2012 Distinct functions of human RECQ helicases WRN and BLM in replication fork recovery and progression after hydroxyurea-induced stalling. DNA repair 63 23253856
2002 Biochemical characterization of the WRN-FEN-1 functional interaction. Biochemistry 62 12356323
2014 Structural mechanisms of human RecQ helicases WRN and BLM. Frontiers in genetics 61 25400656
2008 WRN controls formation of extrachromosomal telomeric circles and is required for TRF2DeltaB-mediated telomere shortening. Molecular and cellular biology 60 18212065
2003 Telomere instability in a human tumor cell line expressing a dominant-negative WRN protein. Human genetics 58 12827497
2008 WRN is required for ATM activation and the S-phase checkpoint in response to interstrand cross-link-induced DNA double-strand breaks. Molecular biology of the cell 56 18596239
2016 Bloom's syndrome: Why not premature aging?: A comparison of the BLM and WRN helicases. Ageing research reviews 55 27238185
2005 The interaction site of Flap Endonuclease-1 with WRN helicase suggests a coordination of WRN and PCNA. Nucleic acids research 55 16326861
2016 CDK1 phosphorylates WRN at collapsed replication forks. Nature communications 54 27634057
2006 Crystal structure of the HRDC domain of human Werner syndrome protein, WRN. The Journal of biological chemistry 53 17148451
2018 HERC2 Facilitates BLM and WRN Helicase Complex Interaction with RPA to Suppress G-Quadruplex DNA. Cancer research 50 30279242
2010 Acetylation of WRN protein regulates its stability by inhibiting ubiquitination. PloS one 48 20428248
2013 Targeting an Achilles' heel of cancer with a WRN helicase inhibitor. Cell cycle (Georgetown, Tex.) 47 24036544
2010 BCR/ABL stimulates WRN to promote survival and genomic instability. Cancer research 46 21123451
2005 p53 modulates RPA-dependent and RPA-independent WRN helicase activity. Cancer research 46 15735006
2000 Cellular Werner phenotypes in mice expressing a putative dominant-negative human WRN gene. Genetics 45 10628995
2012 MYC-driven tumorigenesis is inhibited by WRN syndrome gene deficiency. Molecular cancer research : MCR 44 22301954
2011 The DNA repair endonuclease XPG interacts directly and functionally with the WRN helicase defective in Werner syndrome. Cell cycle (Georgetown, Tex.) 42 21558802
2019 A high-throughput screen to identify novel small molecule inhibitors of the Werner Syndrome Helicase-Nuclease (WRN). PloS one 40 30625228
2011 WRN helicase regulates the ATR-CHK1-induced S-phase checkpoint pathway in response to topoisomerase-I-DNA covalent complexes. Journal of cell science 40 22159421
2018 Nonfunctional mutant Wrn protein leads to neurological deficits, neuronal stress, microglial alteration, and immune imbalance in a mouse model of Werner syndrome. Brain, behavior, and immunity 39 29908963
2017 Werner syndrome (WRN) gene variants and their association with altered function and age-associated diseases. Ageing research reviews 39 29146545
2012 The roles of WRN and BLM RecQ helicases in the Alternative Lengthening of Telomeres. Nucleic acids research 39 22989712
2009 WRN helicase promotes repair of DNA double-strand breaks caused by aberrant mismatch repair of chromium-DNA adducts. Cell cycle (Georgetown, Tex.) 39 19652551
2024 Novel WRN Helicase Inhibitors Selectively Target Microsatellite-Unstable Cancer Cells. Cancer discovery 37 38587317
2014 Rapamycin decreases DNA damage accumulation and enhances cell growth of WRN-deficient human fibroblasts. Aging cell 37 24308646
2006 Werner syndrome and mutations of the WRN and LMNA genes in France. Human mutation 37 16786514
2011 Proteome-wide identification of WRN-interacting proteins in untreated and nuclease-treated samples. Journal of proteome research 36 21210717
2007 Genetic variation in the premature aging gene WRN: a case-control study on breast cancer susceptibility. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 36 17301258
2007 WRN promoter methylation possibly connects mucinous differentiation, microsatellite instability and CpG island methylator phenotype in colorectal cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 36 18084250
2016 Camptothecin targets WRN protein: mechanism and relevance in clinical breast cancer. Oncotarget 35 26959889
2018 Multiple RPAs make WRN syndrome protein a superhelicase. Nucleic acids research 34 29668972
2017 Single-molecule studies reveal reciprocating of WRN helicase core along ssDNA during DNA unwinding. Scientific reports 31 28266653
2002 Distinct proteins encoded by alternative transcripts of the PURG gene, located contrapodal to WRN on chromosome 8, determined by differential termination/polyadenylation. Nucleic acids research 31 12034829
2022 WRN helicase and mismatch repair complexes independently and synergistically disrupt cruciform DNA structures. The EMBO journal 30 36541070
2015 RECQL1 and WRN DNA repair helicases: potential therapeutic targets and proliferative markers against cancers. Frontiers in genetics 30 25620975
2008 Acetylation regulates WRN catalytic activities and affects base excision DNA repair. PloS one 30 18398454
2006 WRN exonuclease activity is blocked by DNA termini harboring 3' obstructive groups. Mechanisms of ageing and development 30 17224176
2011 Non-B DNA-forming sequences and WRN deficiency independently increase the frequency of base substitution in human cells. The Journal of biological chemistry 29 21285356
2006 Enzymatic mechanism of the WRN helicase/nuclease. Methods in enzymology 28 16793395
2016 Replication stress induced site-specific phosphorylation targets WRN to the ubiquitin-proteasome pathway. Oncotarget 27 26695548
2012 Down regulation of miR-124 in both Werner syndrome DNA helicase mutant mice and mutant Caenorhabditis elegans wrn-1 reveals the importance of this microRNA in accelerated aging. Aging 27 23075628
2010 Cooperation of DNA-PKcs and WRN helicase in the maintenance of telomeric D-loops. Aging 27 20519774
2008 Identification and characterization of a Drosophila ortholog of WRN exonuclease that is required to maintain genome integrity. Aging cell 27 18346216
2006 The role of WRN in DNA repair is affected by post-translational modifications. Mechanisms of ageing and development 27 17116323
2018 MDM2-mediated degradation of WRN promotes cellular senescence in a p53-independent manner. Oncogene 26 30532073
2008 Intrinsic ssDNA annealing activity in the C-terminal region of WRN. Biochemistry 26 18771289
2010 WRN participates in translesion synthesis pathway through interaction with NBS1. Mechanisms of ageing and development 25 20600238
2012 Association of epigenetic inactivation of the WRN gene with anticancer drug sensitivity in cervical cancer cells. Oncology reports 24 22797812
2008 WRN Exonuclease activity is blocked by specific oxidatively induced base lesions positioned in either DNA strand. Nucleic acids research 24 18658245
2023 Identification of 2-Sulfonyl/Sulfonamide Pyrimidines as Covalent Inhibitors of WRN Using a Multiplexed High-Throughput Screening Assay. Biochemistry 23 37403936
2022 R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1. International journal of molecular sciences 23 35163467
2021 Pharmacological targeting of differential DNA repair, radio-sensitizes WRN-deficient cancer cells in vitro and in vivo. Biochemical pharmacology 23 33571504
2016 Class I Histone Deacetylase HDAC1 and WRN RECQ Helicase Contribute Additively to Protect Replication Forks upon Hydroxyurea-induced Arrest. The Journal of biological chemistry 23 27672210
2016 WRN-targeted therapy using inhibitors NSC 19630 and NSC 617145 induce apoptosis in HTLV-1-transformed adult T-cell leukemia cells. Journal of hematology & oncology 23 27829440
2012 RECQL5 plays co-operative and complementary roles with WRN syndrome helicase. Nucleic acids research 23 23180761
2022 Clinical prospects of WRN inhibition as a treatment for MSI tumours. NPJ precision oncology 22 36379964
2014 The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers. Oncogene 22 24608430
2014 Strand exchange of telomeric DNA catalyzed by the Werner syndrome protein (WRN) is specifically stimulated by TRF2. Nucleic acids research 22 24880691
2008 Hyperinsulinemia and insulin resistance in Wrn null mice fed a diabetogenic diet. Mechanisms of ageing and development 22 18295300
2007 Depletion of WRN enhances DNA damage in HeLa cells exposed to the benzene metabolite, hydroquinone. Mutation research 22 17875398
2004 RPA alleviates the inhibitory effect of vinylphosphonate internucleotide linkages on DNA unwinding by BLM and WRN helicases. Nucleic acids research 21 15256542
2012 Esophageal cancer risk is associated with polymorphisms of DNA repair genes MSH2 and WRN in Chinese population. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20 22173703
2008 WRN protects against topo I but not topo II inhibitors by preventing DNA break formation. DNA repair 20 18805512
2008 Werner syndrome protein, WRN, protects cells from DNA damage induced by the benzene metabolite hydroquinone. Toxicological sciences : an official journal of the Society of Toxicology 20 19064679
2007 WRN counteracts the NHEJ pathway upon camptothecin exposure. Biochemical and biophysical research communications 20 17303082
2022 WRN promotes bone development and growth by unwinding SHOX-G-quadruplexes via its helicase activity in Werner Syndrome. Nature communications 19 36114168