WRN

This gene encodes a member of the RecQ subfamily of DNA helicase proteins. The encoded nuclear protein is important in the maintenance of genome stability and plays a role in DNA repair, replication, transcription and telomere maintenance. This protein contains a N-terminal 3' to 5' exonuclease domain, an ATP-dependent helicase domain and RQC (RecQ helicase conserved region) domain in its central region, and a C-terminal HRDC (helicase RNase D C-terminal) domain and nuclear localization signal. Defects in this gene are the cause of Werner syndrome, an autosomal recessive disorder characterized by accelerated aging and an elevated risk for certain cancers. [provided by RefSeq, Aug 2017]

Werner Syndrome RecQ Like Helicase

Multifunctional enzyme that has both magnesium and ATP-dependent DNA-helicase activity and 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang. Has no nuclease activity towards single-stranded DNA or blunt-ended double-stranded DNA. Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Important for genomic integrity. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity).
Plays a role in double-strand break repair after gamma-irradiation.

Biological Process aging Source:UniProtKB1 Publication
Biological Process base-excision repair Source:UniProtKB1 Publication
Biological Process brain development Source:Ensembl
Biological Process cellular response to DNA damage stimulus Source:UniProtKB1 Publication
Biological Process cellular response to gamma radiation Source:UniProtKB1 Publication
Biological Process cellular response to starvation Source:MGI1 Publication
Biological Process cellular senescence Source:GO_Central1 Publication
Biological Process DNA duplex unwinding Source:BHF-UCL2 Publications
Biological Process DNA metabolic process Source:UniProtKB1 Publication
Biological Process DNA recombination Source:GO_Central1 Publication
Biological Process DNA repair Source:GO_Central1 Publication
Biological Process DNA replication Source:UniProtKB1 Publication
Biological Process DNA synthesis involved in DNA repair Source:UniProtKB1 Publication
Biological Process DNA unwinding involved in DNA replication Source:GO_Central1 Publication
Biological Process double-strand break repair Source:UniProtKB1 Publication
Biological Process double-strand break repair via homologous recombination Source:GO_Central1 Publication
Biological Process G-quadruplex DNA unwinding Source:BHF-UCL1 Publication
Biological Process multicellular organism aging Source:GO_Central1 Publication
Biological Process positive regulation of hydrolase activity Source:UniProtKB1 Publication
Biological Process positive regulation of strand invasion Source:BHF-UCL1 Publication
Biological Process protein localization to nucleolus Source:MGI1 Publication
Biological Process regulation of growth rate Source:Ensembl
Biological Process replication fork processing Source:UniProtKB1 Publication
Biological Process replicative senescence Source:Ensembl
Biological Process response to oxidative stress Source:UniProtKB1 Publication
Biological Process response to UV-C Source:UniProtKB1 Publication
Biological Process t-circle formation Source:BHF-UCL1 Publication
Biological Process telomere maintenance Source:UniProtKB1 Publication
Biological Process telomere maintenance via semi-conservative replication Source:Reactome
Biological Process telomeric D-loop disassembly Source:BHF-UCL3 Publications

Nucleus, nucleolus
Nucleus
Nucleus, nucleoplasm
Chromosome
Gamma-irradiation leads to its translocation from nucleoli to nucleoplasm and PML regulates the irradiation-induced WRN relocation (PubMed:21639834).
Localizes to DNA damage sites (PubMed:27063109).

Werner syndrome (WRN):
A rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus, ocular cataracts and osteoporosis. The major cause of death, at a median age of 47, is myocardial infarction.
Colorectal cancer (CRC):
A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.

Phosphorylated by PRKDC.