WRN (Werner syndrome, RecQ helicase-like)

2001-03-01   Mounira Amor-Guéret 

Institut Curie - Section de Recherche, UMR 2027 CNRS, Bâtiment 110, Centre Universitaire, F-91405 Orsay Cedex, France





4.4 kb mRNA



1432 amino acids; contains one ATP binding site, one DExH helicase box, one exonuclease domain unique among known RecQ helicases in the N-terminal region, a nuclear localization signal in the C-terminus and a direct repeat of 27 amino acids between the exonuclease and helicase domains.


nuclear, predominant nucleolar localization.


3-5 DNA helicase; 3-5 exonuclease; functionally interacts with DNA polymerase delta (POLD1) and RPA which are required for DNA replication and DNA repair, with Ku which is involved in double strand DNA break repair by non-homologous DNA end joining, and with p53.


Homologous to RecQ helicases, a subfamily of DExH box-containing DNA and RNA helicases. In particular, similarities with the four known human members in the RecQ subfamily, human RecQL, human BLM, the product of the Bloom syndrome gene, and the recently identified human RecQL4, involved in the Rothmund-Thomson syndrome, and RecQL5 proteins



WRN mutations are located over the entire gene and include stop codons, insertions/deletions and exon deletions: not a single missense mutation has been identified so far.

Implicated in

Entity name
Werner syndrome
Uncommon autosomal recessive disorder characterized by early onset of geriatric diseases, including atherosclerosis, osteoporosis, diabetes mellitus, juvenile cataract, graying of the hair and neoplasia, in particular soft-tissue sarcomas, in approximately 10% of WS patients.
WS patients die at mean age 46 +/- 11,6 years due to malignant tumors or cardiovascular infarctions.
Reciprocal chromosomal translocations and extensive genomic deletions.


Pubmed IDLast YearTitleAuthors
105062091999Physical and functional interaction between p53 and the Werner's syndrome protein.Blander G et al
110239992000The Werner syndrome protein contributes to induction of p53 by DNA damage.Blander G et al
107831632000Ku complex interacts with and stimulates the Werner protein.Cooper MP et al
82656661993The gene responsible for Werner syndrome may be a cell division "counting" gene.Faragher RG et al
27623031989Mutator phenotype of Werner syndrome is characterized by extensive deletions.Fukuchi K et al
23032471990Increased frequency of 6-thioguanine-resistant peripheral blood lymphocytes in Werner syndrome patients.Fukuchi K et al
12225851975Variegated translocation mosaicism in human skin fibroblast cultures.Hoehn H et al
107810662000Functional interaction between the Werner Syndrome protein and DNA polymerase delta.Kamath-Loeb AS et al
108805052000Functional interaction between Ku and the werner syndrome protein in DNA end processing.Li B et al
96185081998Nucleolar localization of the Werner syndrome protein in human cells.Marciniak RA et al
102201391999WRN mutations in Werner syndrome.Moser MJ et al
94029541997An apoptosis-inducing genotoxin differentiates heterozygotic carriers for Werner helicase mutations from wild-type and homozygous mutants.Ogburn CE et al
109828872000Telomere repeat DNA forms a large non-covalent complex with unique cohesive properties which is dissociated by Werner syndrome DNA helicase in the presence of replication protein A.Ohsugi I et al
89687421996Homozygous and compound heterozygous mutations at the Werner syndrome locus.Oshima J et al
110273362000Werner protein recruits DNA polymerase delta to the nucleolus.Szekely AM et al
83573451993Werner syndrome and biological ageing: a molecular genetic hypothesis.Thweatt R et al
106151192000Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts.Wyllie FS et al
96977001998Replication focus-forming activity 1 and the Werner syndrome gene product.Yan H et al
86025091996Positional cloning of the Werner's syndrome gene.Yu CE et al

Other Information

Locus ID:

NCBI: 7486
MIM: 604611
HGNC: 12791
Ensembl: ENSG00000165392


dbSNP: 7486
ClinVar: 7486
TCGA: ENSG00000165392


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
SUMO E3 ligases SUMOylate target proteinsREACTOMER-HSA-3108232
SUMOylation of DNA damage response and repair proteinsREACTOMER-HSA-3108214
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
Cell CycleREACTOMER-HSA-1640170
Cell Cycle CheckpointsREACTOMER-HSA-69620
G2/M CheckpointsREACTOMER-HSA-69481
G2/M DNA damage checkpointREACTOMER-HSA-69473
DNA Double-Strand Break RepairREACTOMER-HSA-5693532
Homology Directed RepairREACTOMER-HSA-5693538
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)REACTOMER-HSA-5693567
Processing of DNA double-strand break endsREACTOMER-HSA-5693607
HDR through Homologous Recombination (HRR)REACTOMER-HSA-5685942
Homologous DNA Pairing and Strand ExchangeREACTOMER-HSA-5693579
Presynaptic phase of homologous DNA pairing and strand exchangeREACTOMER-HSA-5693616
Resolution of D-Loop StructuresREACTOMER-HSA-5693537
Resolution of D-loop Structures through Holliday Junction IntermediatesREACTOMER-HSA-5693568
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)REACTOMER-HSA-5693554
HDR through Single Strand Annealing (SSA)REACTOMER-HSA-5685938
Regulation of TP53 ActivityREACTOMER-HSA-5633007
Regulation of TP53 Activity through PhosphorylationREACTOMER-HSA-6804756

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
155912072004Defective telomere lagging strand synthesis in cells lacking WRN helicase activity.252
121813132002Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases.137
122422782002Homologous recombination resolution defect in werner syndrome.107
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
160300112005POT1 stimulates RecQ helicases WRN and BLM to unwind telomeric DNA substrates.80
182506212008The RecQ helicase WRN is required for normal replication fork progression after DNA damage or replication fork arrest.80
167233992006Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer.79
251227542014DNA2 cooperates with the WRN and BLM RecQ helicases to mediate long-range DNA end resection in human cells.68
158455382005RecQ family members combine strand pairing and unwinding activities to catalyze strand exchange.67
185249932008Up-regulation of WRN and DNA ligase IIIalpha in chronic myeloid leukemia: consequences for the repair of DNA double-strand breaks.66


Mounira Amor-Guéret

WRN (Werner syndrome, RecQ helicase-like)

Atlas Genet Cytogenet Oncol Haematol. 2001-03-01

Online version: http://atlasgeneticsoncology.org/gene/284/wrn-(werner-syndrome-recq-helicase-like)