GenAge entry for WRN (Homo sapiens)

Entry selected based on evidence directly linking the gene product to ageing in humans

Gene name (HAGRID: 13)

HGNC symbol: WRN
Aliases: RECQL2; RECQ3
Common name: Werner syndrome, RecQ helicase-like

Potential relevance to the human ageing process

Main reason for selection

Entry selected based on evidence directly linking the gene product to ageing in humans

Description

Werner syndrome (WS), caused by mutations in WRN, is probably the most dramatic segmental progeroid syndrome. Although there are differences between the pathobiology of normal ageing and the phenotype of WS, the age-related changes of WS patients are remarkably similar to those found during normal ageing, only they occur at earlier ages [56]. WRN is one of the strongest candidates for genes influencing human ageing.

WRN-deficient mice display reduced embryonic survival, increased tumour formation, and their fibroblasts show features similar to those found in fibroblasts derived from WS patients such as a premature loss of proliferative capacity, though their ageing process appears unaltered [730]. In late-generation mice without TERC, and hence with short telomeres, WRN mutations result in a phenotype resembling accelerated ageing somewhat reminiscent from WS [1069].

WRN is a helicase and exonuclease involved in many DNA repair and processing pathways [1265]. Genetic variation studies in breast cancer patients, showed that WRN might have an important tumorigenic role [3648]. Human WRN-null mesenchymal stem cells show several features associated with accelerated aging [4332]. These include increased senescence associated markers, activation of the senescence-associated secretory phenotype and an increased DNA damage response. In addition, there is a global loss of H3K9me3 and accompanying changes in heterochromatin architecture. It was shown that WRN associates with heterochromatin proteins SUV39H1 and HP1a and nuclear lamina-heterochromatin anchoring protein LAP2b [4332]. Thus, WRN may play a role in maintaining heterochromatin stability as part of its role in the ageing process.

Cytogenetic information

Cytogenetic band: 8p12
Location: 31,033,262 bp to 31,173,761 bp
Orientation: Plus strand

Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology

Process:

GO:0000722; telomere maintenance via recombination
GO:0000723; telomere maintenance
GO:0000731; DNA synthesis involved in DNA repair
GO:0000732; strand displacement
GO:0001302; replicative cell aging
GO:0006259; DNA metabolic process
GO:0006260; DNA replication
GO:0006284; base-excision repair
GO:0006302; double-strand break repair
GO:0006974; cellular response to DNA damage stimulus
GO:0006979; response to oxidative stress
GO:0007420; brain development
GO:0007568; aging
GO:0007569; cell aging
GO:0009267; cellular response to starvation
GO:0010225; response to UV-C
GO:0010259; multicellular organism aging
GO:0016925; protein sumoylation
GO:0031297; replication fork processing
GO:0032066; nucleolus to nucleoplasm transport
GO:0032508; DNA duplex unwinding
GO:0040009; regulation of growth rate
GO:0042981; regulation of apoptotic process
GO:0051345; positive regulation of hydrolase activity
GO:0071480; cellular response to gamma radiation
GO:0090305; nucleic acid phosphodiester bond hydrolysis
GO:1901796; regulation of signal transduction by p53 class mediator

Cellular component:

GO:0000784; nuclear chromosome, telomeric region
GO:0005654; nucleoplasm
GO:0005730; nucleolus
GO:0005737; cytoplasm
GO:0005813; centrosome
GO:0032389; MutLalpha complex
GO:0043005; neuron projection

Function:

GO:0000287; magnesium ion binding
GO:0000403; Y-form DNA binding
GO:0000405; bubble DNA binding
GO:0003677; DNA binding
GO:0003678; DNA helicase activity
GO:0003682; chromatin binding
GO:0004003; ATP-dependent DNA helicase activity
GO:0004386; helicase activity
GO:0004527; exonuclease activity
GO:0005515; protein binding
GO:0005524; ATP binding
GO:0008408; 3'-5' exonuclease activity
GO:0009378; four-way junction helicase activity
GO:0016887; ATPase activity
GO:0030145; manganese ion binding
GO:0032403; protein complex binding
GO:0042803; protein homodimerization activity
GO:0043138; 3'-5' DNA helicase activity
GO:0043140; ATP-dependent 3'-5' DNA helicase activity
GO:0051880; G-quadruplex DNA binding

Hide GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge: TP53, ATM, WRN, NBN, PARP1, CREBBP, RPA1, BLM, VCP, RAD51, PML, PRKDC, XRCC5, PCNA, FEN1, TERF2, XRCC6, RAD52, SIRT1, SUMO1, H2AFX, CDKN2A, ATR, POLB
STRING interaction network

Retrieve sequences for WRN

Promoter: Promoter
ORF: ORF
CDS: CDS

Homologs in model organisms

Caenorhabditis elegans: wrn-1
Danio rerio: wrn
Mus musculus: Wrn
Rattus norvegicus: Wrn
Saccharomyces cerevisiae: SGS1

In other databases

GenAge model organism genes

A homolog of this gene for Saccharomyces cerevisiae is present as SGS1

LongevityMap

This gene is present as WRN

CellAge

This gene is present as WRN