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WRN

Identity

HGNC (Hugo) WRN
Location 8p12
Location_base_pair Starts at 31010320 and ends at 31150819 bp from pter ( according to hg18-Mar_2006)  [Mapping]

DNA/RNA

Transcription 4.4 kb mRNA

Protein

Description 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.
Localisation nuclear, predominant nucleolar localization.
Function 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.
Homology 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

Mutations

Germinal 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 Werner syndrome
Disease 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.
Prognosis WS patients die at mean age 46 +/- 11,6 years due to malignant tumors or cardiovascular infarctions.
Cytogenetics Reciprocal chromosomal translocations and extensive genomic deletions.
  

External links

Nomenclature
HGNC (Hugo)WRN   12791
Entrez_Gene (NCBI)WRN  7486  Werner syndrome
Cards
AtlasWRNID284
GeneCards (Weizmann)WRN
Ensembl (Hinxton)ENSG00000165392 [Gene_View]  WRN [Vega]
AceView (NCBI)WRN
Genatlas (Paris)WRN
euGene (Indiana)7486
SOURCE (Stanford)NM_000553
Genomic and cartography
GoldenPath (UCSC)WRN  -  8p12   chr8:31010320-31150819 +  8p12   [Description]    (hg18-Mar_2006)
EnsemblWRN - 8p12 [CytoView]
Mapping of homologs : NCBIWRN [Mapview]
OMIM277700   604611   
Gene and transcription
Gene : Genbank (Entrez)AB209652 AF091214 AL833572 AY818673 BP279291
Reference sequence (RefSeq transcript) :SRSNM_000553
Reference transcript : EntrezNM_000553
RefSeq genomic : SRSAC_000051 AC_000140 NC_000008 NG_008870 NT_007995 NW_001839128 NW_923907
RefSeq genomic : EntrezAC_000051 AC_000140 NC_000008 NG_008870 NT_007995 NW_001839128 NW_923907
Consensus coding sequences : CCDS NCBIWRN
Cluster EST : UnigeneHs.632050 [ SRS ] Hs.632050 [ NCBI ]
Alternative Splicing : Fast-db (Paris)3441
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtQ14191 (SRS) Q14191 (Expasy) Q14191 (Uniprot)
With graphics : InterProQ14191
Splice isoforms : VarSplice FASTAQ14191(VarSplice FASTA)
Domaine pattern : Prosite (SRS)DEAH_ATP_HELICASE (PS00690)    HELICASE_ATP_BIND_1 (PS51192)    HELICASE_CTER (PS51194)    HRDC (PS50967)   
Domain pattern : Prosite (Expaxy)DEAH_ATP_HELICASE (PS00690)    HELICASE_ATP_BIND_1 (PS51192)    HELICASE_CTER (PS51194)    HRDC (PS50967)   
Domains : Interpro (SRS)3_5_exonuclease    DEAD-like_N    DNA/RNA_helicase_C    DNA/RNA_helicase_DEAD/DEAH_N    DNA/RNA_helicase_DEAH_CS    DNA_helicase_ATP-dep_RecQ    Helicase_SF1/SF2_ATP-bd    HRDC   
Domains : Interpro (EBI)3_5_exonuclease    DEAD-like_N    DNA/RNA_helicase_C    DNA/RNA_helicase_DEAD/DEAH_N    DNA/RNA_helicase_DEAH_CS    DNA_helicase_ATP-dep_RecQ    Helicase_SF1/SF2_ATP-bd    HRDC   
Related proteins : CluSTrQ14191
Domain families : Pfam SRS3_5_exonuc (PF01612)    DEAD (PF00270)    Helicase_C (PF00271)    HRDC (PF00570)   
Domain families : Pfam Sanger3_5_exonuc (PF01612)    DEAD (PF00270)    Helicase_C (PF00271)    HRDC (PF00570)   
Domain families : Pfam NCBIpfam01612    pfam00270    pfam00271    pfam00570   
Domain families : Smart EMBL35EXOc (SM00474)DEXDc (SM00487)HELICc (SM00490)HRDC (SM00341)
Blocks (Seattle)Q14191
Crystal structure of protein : PDB SRS2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0   
Crystal structure of protein : PDBSum2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0   
Crystal structure of protein : IMB2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0   
Crystal structure of protein : PDB RSDB2AXL    2DGZ    2E1E    2E1F    2FBT    2FBV    2FBX    2FBY    2FC0   
HPRD05212
Protein Interaction databases
DIP (DOE-UCLA)Q14191
IntAct (EBI)Q14191
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIWRN
SNP : GeneSNP UtahWRN
SNP : HGBaseWRN
Genetic variants : HAPMAPWRN
Somatic Mutations in Cancer : COSMICWRN 
OrphanetWerner syndrome
Mutations and Diseases : HGMDWRN
Hereditary diseases : OMIM277700    604611   
Hereditary diseases : GENETests277700    604611   
Diseases : Genetic AssociationWRN
General knowledge
Homologs : HomoloGeneWRN
Homology/Alignments : Family Browser UCSCWRN
Phylogenetic Trees/Animal Genes : TreeFamWRN
Chemical/Protein Interactions : CTD7486
Keywords Ontology : AmiGOnucleotide binding  Y-form DNA binding  bubble DNA binding  telomere maintenance  DNA synthesis during DNA repair  replicative cell aging  DNA binding  ATP binding  intracellular  nucleus  nucleoplasm  nucleolus  centrosome  base-excision repair  DNA recombination  response to DNA damage stimulus  response to oxidative stress  3'-5' exonuclease activity  four-way junction helicase activity  response to UV-C  multicellular organismal aging  hydrolase activity  ATPase activity  replication fork processing  replication fork processing  MutLalpha complex  protein complex binding  regulation of growth rate  protein homodimerization activity  regulation of apoptosis  ATP-dependent 3'-5' DNA helicase activity  positive regulation of hydrolase activity  G-quadruplex DNA binding  
Keywords Ontology : EGO-EBInucleotide binding  Y-form DNA binding  bubble DNA binding  telomere maintenance  DNA synthesis during DNA repair  replicative cell aging  DNA binding  ATP binding  intracellular  nucleus  nucleoplasm  nucleolus  centrosome  base-excision repair  DNA recombination  response to DNA damage stimulus  response to oxidative stress  3'-5' exonuclease activity  four-way junction helicase activity  response to UV-C  multicellular organismal aging  hydrolase activity  ATPase activity  replication fork processing  replication fork processing  MutLalpha complex  protein complex binding  regulation of growth rate  protein homodimerization activity  regulation of apoptosis  ATP-dependent 3'-5' DNA helicase activity  positive regulation of hydrolase activity  G-quadruplex DNA binding  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Other databasehttp://www.ncbi.nlm.nih.gov/cgi-bin/SCIENCE96/gene?WRN
Probes
Probes : ImagenesWRN Related clones (RZPD - Berlin)
Literature
PubMed149 Pubmed reference(s) in Entrez
PubGeneWRN

Bibliography

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PMID 1222585
 
Mutator phenotype of Werner syndrome is characterized by extensive deletions.
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PMID 2762303
 
Increased frequency of 6-thioguanine-resistant peripheral blood lymphocytes in Werner syndrome patients.
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PMID 2303247
 
The gene responsible for Werner syndrome may be a cell division counting gene.
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Homozygous and compound heterozygous mutations at the Werner syndrome locus.
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Positional cloning of the Werner's syndrome gene.
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An apoptosis-inducing genotoxin differentiates heterozygotic carriers for Werner helicase mutations from wild-type and homozygous mutants.
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Nucleolar localization of the Werner syndrome protein in human cells.
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PMID 9618508
 
WRN mutations in Werner syndrome.
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PMID 10220139
 
Replication focus-forming activity 1 and the Werner syndrome gene product.
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Nature genetics. 1998 ; 19 (4) : 375-378.
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Physical and functional interaction between p53 and the Werner's syndrome protein.
Blander G, Kipnis J, Leal JF, Yu CE, Schellenberg GD, Oren M
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PMID 10506209
 
Functional interaction between the Werner Syndrome protein and DNA polymerase delta.
Kamath-Loeb AS, Johansson E, Burgers PM, Loeb LA
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (9) : 4603-4608.
PMID 10781066
 
Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts.
Wyllie FS, Jones CJ, Skinner JW, Haughton MF, Wallis C, Wynford-Thomas D, Faragher RG, Kipling D
Nature genetics. 2000 ; 24 (1) : 16-17.
PMID 10615119
 
Ku complex interacts with and stimulates the Werner protein.
Cooper MP, Machwe A, Orren DK, Brosh RM, Ramsden D, Bohr VA
Genes & development. 2000 ; 14 (8) : 907-912.
PMID 10783163
 
Functional interaction between Ku and the werner syndrome protein in DNA end processing.
Li B, Comai L
The Journal of biological chemistry. 2000 ; 275 (37) : 28349-28352.
PMID 10880505
 
The Werner syndrome protein contributes to induction of p53 by DNA damage.
Blander G, Zalle N, Leal JF, Bar-Or RL, Yu CE, Oren M
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Werner protein recruits DNA polymerase delta to the nucleolus.
Szekely AM, Chen YH, Zhang C, Oshima J, Weissman SM
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PMID 11027336
 
Telomere 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.
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PMID 10982887
 
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Contributor(s)

Written03-2001Mounira Amor-Guéret
Institut Curie - Section de Recherche, UMR 2027 CNRS, Bātiment 110, Centre Universitaire, F-91405 Orsay Cedex, France

Citation

This paper should be referenced as such :
Amor-Guéret M . WRN. Atlas Genet Cytogenet Oncol Haematol. March 2001 .
URL : http://AtlasGeneticsOncology.org/Genes/WRNID284.html

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indexed on : Sat Jun 27 16:39:54 CEST 2009

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