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A mislocalization of the Wrn mutant protein in the liver endoplasmic reticulum fraction increased oxidative stress in that cellular compartment. Vitamin C reversed this oxidative stress.
The deleterious effects of the helicase-deficient Wrn protein are mediated by the dysfunction of several cellular organelles.
Data suggest that, in the context of Wrn deficiency-related telomere dysfunction, loss of p16Ink4a function could prevent cells from senescence.
The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers.
Studies show that in the context of Myc-associated tumorigenesis, loss of Wrn amplifies the DNA damage response, both in preneoplastic and neoplastic tissue, engaging activation of tumor suppressor pathways.
embryonic fibroblasts lacking a functional Wrn helicase (show DNA2 ELISA Kits) inhibited the immortalization of Safb1 (show SAFB ELISA Kits)-null cells. These results indicate that an intact Wrn protein is required for immortalization and tumorigenesis in Safb1 (show SAFB ELISA Kits)-null mice.
BCR/ABL-mediated stimulation of WRN modulates the efficiency and fidelity of major DSB repair mechanisms to protect leukemia cells from apoptosis and to facilitate genomic instability.
WRN has a role in processing specific types of homologous recombination intermediates as well as an important function in nonhomologous recombination
results demonstrate that WRN loss confers a strong cellular phenotype in early passage human - though not mouse - primary fibroblasts.
Genetic cooperation between this protein and poly(ADP-ribose) polymerase-1 (show PARP1 ELISA Kits) prevent chromatid breaks, complex chromosomal rearrangements, and cancer in mice.
The WRN Cys1367Arg (T>C) polymorphism is not associated with overall cancer risk, although subgroup analyses suggested an association with breast cancer and overall cancer specifically in European populations. [meta-analysis]
The CC genotype of WRN rs1346044 may contribute to an increased risk and a premature onset of breast cancer.
Japanese subjects bearing at least one A allele of rs2230009 of the WRN gene are at a significantly higher risk of femoral fracture, possibly due to decreased bone density.
WRN prefers to act on DNA strand invasion intermediates in a manner that favours strand invasion and exchange.
we provide a proof of concept for applying the external guide sequence (EGS) approach in directing an RNase P RNA to efficiently cleave the WRN mRNA in cultured human cell lines.
Multiplex genetic testing of 90 cancer susceptibility genes disclosed a novel WRN frameshift mutation (p.N1370Tfs*23) in a mother and her 2 (show ERBB2 ELISA Kits) daughters with cancer and in the youngest unaffected daughter.
PARylation is involved in the recruitment of RECQL5 and WRN to laser-induced DNA damage and RECQL5 and WRN have differential responses to PARylated PARP1 and Poly(ADP-ribose).
WRN knockdown decreased the G(O):A-induced A:T --> C:G mutations, suggesting that WRN may enhance the mutations caused by G(O) in the nucleotide pool
a significant interaction with risk of overall Non Hodgkin lymphoma was observed between WRN rs1346044 and hair dye use before 1980.
knockdown of WRN reduced TNF-alpha (show TNF ELISA Kits) stimulation-induced activation of the endogenous promoter of IL-8 (show IL8 ELISA Kits), an NF-kappaB (show NFKB1 ELISA Kits)-responsive gene, and WRN increased its association with the IL-8 (show IL8 ELISA Kits) promoter region together with RelA (show NFkBP65 ELISA Kits)/p50 (show CD40 ELISA Kits) after TNF-alpha (show TNF ELISA Kits) stimulation
This gene encodes a member of the RecQ subfamily and the DEAH (Asp-Glu-Ala-His) subfamily of DNA and RNA helicases. DNA helicases are involved in many aspects of DNA metabolism, including transcription, replication, recombination, and repair. This protein contains a nuclear localization signal in the C-terminus and shows a predominant nucleolar localization. It possesses an intrinsic 3' to 5' DNA helicase activity, and is also a 3' to 5' exonuclease. Based on interactions between this protein and Ku70/80 heterodimer in DNA end processing, this protein may be involved in the repair of double strand DNA breaks. Defects in this gene are the cause of Werner syndrome, an autosomal recessive disorder characterized by premature aging.
, Werner syndrome ATP-dependent helicase homolog
, exonuclease WRN
, DNA helicase, RecQ-like type 3
, Werner syndrome ATP-dependent helicase
, recQ protein-like 2