WRN

Identity

Hugo	WRN
Location	8p12

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
Hugo	WRN
GDB	WRN
Entrez_Gene	WRN  7486  Werner syndrome
	Cards
Atlas	WRNID284
GeneCards	WRN
Ensembl	WRN [Search_View]   ENSG00000165392 [Gene_View]
Genatlas	WRN
GeneLynx	WRN
eGenome	WRN
euGene	7486
	Genomic and cartography
GoldenPath	WRN  -  8p12   chr8:31010320-31150818 +  8p12-p11.2   [Description]    (hg18-Mar_2006)
Ensembl	WRN - 8p12-p11.2 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	WRN
	Gene and transcription
Genbank	AB209652 [ ENTREZ ]
Genbank	AF091214 [ ENTREZ ]
Genbank	AL833572 [ ENTREZ ]
Genbank	AY818673 [ ENTREZ ]
RefSeq	NM_000553 [ SRS ]    NM_000553 [ ENTREZ ]
RefSeq	AC_000051 [ SRS ]    AC_000051 [ ENTREZ ]
RefSeq	NC_000008 [ SRS ]    NC_000008 [ ENTREZ ]
RefSeq	NT_007995 [ SRS ]    NT_007995 [ ENTREZ ]
RefSeq	NW_923907 [ SRS ]    NW_923907 [ ENTREZ ]
AceView	WRN AceView - NCBI
Unigene	Hs.632050 [ SRS ]    Hs.632050 [ NCBI ]     HS632050 [ spliceNest ]
Fast-db	3441 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q14191 [ SRS]    Q14191 [ EXPASY ]     Q14191 [ INTERPRO ]
Prosite	PS00690 DEAH_ATP_HELICASE [ SRS ]    PS00690 DEAH_ATP_HELICASE [ Expasy ]
Prosite	PS51192 HELICASE_ATP_BIND_1 [ SRS ]    PS51192 HELICASE_ATP_BIND_1 [ Expasy ]
Prosite	PS51194 HELICASE_CTER [ SRS ]    PS51194 HELICASE_CTER [ Expasy ]
Prosite	PS50967 HRDC [ SRS ]    PS50967 HRDC [ Expasy ]
Interpro	IPR002562 3_5_exonuclease [ SRS ]    IPR002562 3_5_exonuclease [ EBI ]
Interpro	IPR014001 DEAD-like_N [ SRS ]    IPR014001 DEAD-like_N [ EBI ]
Interpro	IPR001650 DNA/RNA_helicase_C [ SRS ]    IPR001650 DNA/RNA_helicase_C [ EBI ]
Interpro	IPR011545 DNA/RNA_helicase_DEAD/DEAH_N [ SRS ]    IPR011545 DNA/RNA_helicase_DEAD/DEAH_N [ EBI ]
Interpro	IPR002464 DNA/RNA_helicase_DEAH_CS [ SRS ]    IPR002464 DNA/RNA_helicase_DEAH_CS [ EBI ]
Interpro	IPR004589 DNA_helicase_ATP-dep_RecQ [ SRS ]    IPR004589 DNA_helicase_ATP-dep_RecQ [ EBI ]
Interpro	IPR014021 Helicase_SF1/SF2_ATP-bd [ SRS ]    IPR014021 Helicase_SF1/SF2_ATP-bd [ EBI ]
Interpro	IPR002121 HRDC [ SRS ]    IPR002121 HRDC [ EBI ]
CluSTr	Q14191
Pfam	PF01612 3_5_exonuc [ SRS ]    PF01612 3_5_exonuc [ Sanger ]    pfam01612 [ NCBI-CDD ]
Pfam	PF00270 DEAD [ SRS ]    PF00270 DEAD [ Sanger ]    pfam00270 [ NCBI-CDD ]
Pfam	PF00271 Helicase_C [ SRS ]    PF00271 Helicase_C [ Sanger ]    pfam00271 [ NCBI-CDD ]
Pfam	PF00570 HRDC [ SRS ]    PF00570 HRDC [ Sanger ]    pfam00570 [ NCBI-CDD ]
Smart	SM00474 35EXOc [EMBL]
Smart	SM00487 DEXDc [EMBL]
Smart	SM00490 HELICc [EMBL]
Smart	SM00341 HRDC [EMBL]
Blocks	Q14191
PDB	2AXL [ SRS ]    2AXL [ PdbSum ],   2AXL [ IMB ]   2AXL [ RSDB ]
PDB	2DGZ [ SRS ]    2DGZ [ PdbSum ],   2DGZ [ IMB ]   2DGZ [ RSDB ]
PDB	2E1E [ SRS ]    2E1E [ PdbSum ],   2E1E [ IMB ]   2E1E [ RSDB ]
PDB	2E1F [ SRS ]    2E1F [ PdbSum ],   2E1F [ IMB ]   2E1F [ RSDB ]
PDB	2FBT [ SRS ]    2FBT [ PdbSum ],   2FBT [ IMB ]   2FBT [ RSDB ]
PDB	2FBV [ SRS ]    2FBV [ PdbSum ],   2FBV [ IMB ]   2FBV [ RSDB ]
PDB	2FBX [ SRS ]    2FBX [ PdbSum ],   2FBX [ IMB ]   2FBX [ RSDB ]
PDB	2FBY [ SRS ]    2FBY [ PdbSum ],   2FBY [ IMB ]   2FBY [ RSDB ]
PDB	2FC0 [ SRS ]    2FC0 [ PdbSum ],   2FC0 [ IMB ]   2FC0 [ RSDB ]
HPRD	05212
	Protein Interaction databases
DIP	Q14191
IntAct	Q14191
	Polymorphism : SNP, mutations, diseases
OMIM	277700;604611    [ map ]
GENECLINICS	277700;604611
SNP	WRN [dbSNP-NCBI]
SNP	NM_000553 [SNP-NCI]
SNP	WRN [GeneSNPs - Utah]  WRN] [HGBASE - SRS]
HAPMAP	WRN [HAPMAP]
COSMIC	WRN [Somatic mutation (COSMIC-CGP-Sanger)]
Orphanet	Werner syndrome
HGMD	WRN
	General knowledge
Family Browser	WRN [UCSC Family Browser]
SOURCE	NM_000553
SMD	Hs.632050
SAGE	Hs.632050
Enzyme	3.6.1.- [ Enzyme-SRS ]   3.6.1.- [ Brenda-SRS ]   3.6.1.- [ KEGG ]   3.6.1.- [ WIT ]
GO	nucleotide binding [Amigo]  nucleotide binding
GO	telomere maintenance [Amigo]  telomere maintenance
GO	replicative cell aging [Amigo]  replicative cell aging
GO	DNA binding [Amigo]  DNA binding
GO	DNA helicase activity [Amigo]  DNA helicase activity
GO	protein binding [Amigo]  protein binding
GO	ATP binding [Amigo]  ATP binding
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	nucleoplasm [Amigo]  nucleoplasm
GO	nucleolus [Amigo]  nucleolus
GO	nucleobase, nucleoside, nucleotide and nucleic acid metabolic process [Amigo]  nucleobase, nucleoside, nucleotide and nucleic acid metabolic process
GO	DNA replication [Amigo]  DNA replication
GO	DNA recombination [Amigo]  DNA recombination
GO	ATP-dependent helicase activity [Amigo]  ATP-dependent helicase activity
GO	3'-5' exonuclease activity [Amigo]  3'-5' exonuclease activity
GO	multicellular organismal aging [Amigo]  multicellular organismal aging
GO	hydrolase activity [Amigo]  hydrolase activity
GO	regulation of growth rate [Amigo]  regulation of growth rate
GO	regulation of apoptosis [Amigo]  regulation of apoptosis
PubGene	WRN
TreeFam	WRN
CTD	7486 [Comparative ToxicoGenomics Database]
	Other databases
Other database	http://www.ncbi.nlm.nih.gov/cgi-bin/SCIENCE96/gene?WRN
	Probes
Probe	WRN Related clones (RZPD - Berlin)
	PubMed
PubMed	106 Pubmed reference(s) in LocusLink

Bibliography

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Cytogenetics and cell genetics. 1975 ; 15 (5) : 282-298.

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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Human genetics. 1990 ; 84 (3) : 249-252.

PMID 2303247

The gene responsible for Werner syndrome may be a cell division counting gene.

Faragher RG, Kill IR, Hunter JA, Pope FM, Tannock C, Shall S

Proceedings of the National Academy of Sciences of the United States of America. 1993 ; 90 (24) : 12030-12034.

PMID 8265666

Werner syndrome and biological ageing: a molecular genetic hypothesis.

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PMID 8357345

Homozygous and compound heterozygous mutations at the Werner syndrome locus.

Oshima J, Yu CE, Piussan C, Klein G, Jabkowski J, Balci S, Miki T, Nakura J, Ogihara T, Ells J, Smith M, Melaragno MI, Fraccaro M, Scappaticci S, Matthews J, Ouais S, Jarzebowicz A, Schellenberg GD, Martin GM

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PMID 8968742

Positional cloning of the Werner's syndrome gene.

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PMID 8602509

An apoptosis-inducing genotoxin differentiates heterozygotic carriers for Werner helicase mutations from wild-type and homozygous mutants.

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PMID 9402954

Nucleolar localization of the Werner syndrome protein in human cells.

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Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (12) : 6887-6892.

PMID 9618508

WRN mutations in Werner syndrome.

Moser MJ, Oshima J, Monnat RJ Jr

Human mutation. 1999 ; 13 (4) : 271-279.

PMID 10220139

Replication focus-forming activity 1 and the Werner syndrome gene product.

Yan H, Chen CY, Kobayashi R, Newport J

Nature genetics. 1998 ; 19 (4) : 375-378.

PMID 9697700

Physical and functional interaction between p53 and the Werner's syndrome protein.

Blander G, Kipnis J, Leal JF, Yu CE, Schellenberg GD, Oren M

The Journal of biological chemistry. 1999 ; 274 (41) : 29463-29469.

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

The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2000 ; 14 (14) : 2138-2140.

PMID 11023999

Werner protein recruits DNA polymerase delta to the nucleolus.

Szekely AM, Chen YH, Zhang C, Oshima J, Weissman SM

Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (21) : 11365-11370.

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.

Ohsugi I, Tokutake Y, Suzuki N, Ide T, Sugimoto M, Furuichi Y

Nucleic acids research. 2000 ; 28 (18) : 3642-3648.

PMID 10982887

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Contributor(s)

Written	03-2001	Mounira 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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:28:01 2008