Recombinant Human Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN (WRN), partial

1. results indicate that WRN helicase activity alone is not rate-limiting for the development of clinical Werner syndrome. PMID: 28276523
2. The acidic domain of WRNp was shown to affect the transcription of certain proteins involved in autophagy and aging. PMID: 29800817
3. Data suggest that Werner syndrome helicase (WRN) promotes classical (c)-nonhomologous end joining (NHEJ) via helicase and exonuclease activities and inhibits alternative (alt)-NHEJ using non-enzymatic functions. PMID: 27922005
4. A CDK1-dependent regulation of the WRN-DNA2-mediated resection and identify a new function of WRN as a DSB repair pathway switch are reported. PMID: 27634057
5. In the Title. PMID: 28012115
6. Data show that helicases RHAU, BLM, and WRN exhibit distinct G-quadruplex (GQ) conformation specificity, but use a common mechanism of repetitive unfolding that leads to disrupting GQ structure multiple times in succession. PMID: 27407146
7. there was no consistent association between WRN promoter hypermethylation and loss of WRN expression at the mRNA or protein level in CRC cell lines or tumors. PMID: 27121793
8. Low WRN expression is associated with aggressive tumor phenotype in breast cancer. PMID: 26959889
9. WRN is essential for survival of ATLL cells PMID: 27829440
10. The authors show that the helicase of hDNA2 functionally integrates with BLM or WRN helicases to promote double-stranded DNA degradation by forming a heterodimeric molecular machine. This collectively suggests that the human DNA2 motor promotes the enzyme's capacity to degrade double-stranded DNA in conjunction with BLM or WRN and thus promote the repair of broken DNA. PMID: 27612385
11. In meta-analyses including 59,190 individuals in 5 studies, the hazard ratio for ischemic stroke for C1367R TT homozygotes versus CC/CT was 1.14 . The study suggests that common genetic variation in WRN is associated with increased risk of ischemic stroke in the general population. PMID: 28063943
12. The findings suggest that the epidermis is among the tissue types that do not display symptoms of premature ageing caused by loss of function of wrn. This is in support that Werner's syndrome is a segmental progeroid syndrome. PMID: 27492502
13. Active control of repetitive structural transitions between replication forks and Holliday junctions by WRN has been reported. PMID: 27427477
14. Evaluation of localization of WRN signals demonstrated that WRN does not leave the nucleolus after irradiation. The WRN signal was not detected at the telomere sides, but H2AX was detected at the telomeric sides. Thus, the WRN protein is not involved in irradiation-induced DNA damage/repair, even at telomeric sides in human mesenchymal stem cells (hMSC) and hMSC-telomere 1. PMID: 28436335
15. The proportion of compound heterozygotes (31.8%) was significantly greater than reported previously (14.2%), indicating that the incidence of consanguineous marriage of parents has decreased. One novel mutant allele was identified in an individual with the compound heterozygous genotype. PMID: 28394436
16. In humans, mutations in WRN give rise to Werner syndrome characterized by premature development of features associated with aging. PMID: 27238185
17. Werner syndrome is a prototypical segmental progeroid syndrome characterized by multiple features consistent with accelerated aging. It is caused by null mutations of the WRN gene, which encodes a member of the RECQ family of DNA helicases. PMID: 26993153
18. Our results identify the human WRN RECQ protein as a G4 helicase that modulates gene expression in G4-dependent fashion at many chromosomal sites and provide several new and unexpected mechanistic insights into Werner syndrome (WS) disease pathogenesis PMID: 26984941
19. WRN or the Bloom syndrome helicase (BLM) stimulates DNA polymerase delta progression across telomeric G-rich repeats, only WRN promotes sequential strand displacement synthesis and FEN1 cleavage. PMID: 27849570
20. This study identified residues in the WRN RQC domain that are involved specifically in the interaction with G-quadruplex DNA. PMID: 28069813
21. findings indicate that WRN interacts with HDACs 1 and 2 to facilitate activity of stalled replication forks under conditions of replication stress. PMID: 27672210
22. We found statistically significant association with AAO for three genes (WRN, NTN4 and LAMC3) with common associated variants. PMID: 26394601
23. Finfings indicate a role for Werner syndrome helicase WRN as a modulator of DNA repair, replication, and recombination. PMID: 26695548
24. 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] PMID: 25468760
25. The CC genotype of WRN rs1346044 may contribute to an increased risk and a premature onset of breast cancer. PMID: 26690424
26. 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. PMID: 25637295
27. WRN prefers to act on DNA strand invasion intermediates in a manner that favours strand invasion and exchange. PMID: 26420422
28. 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. PMID: 26808708
29. Multiplex genetic testing of 90 cancer susceptibility genes disclosed a novel WRN frameshift mutation (p.N1370Tfs*23) in a mother and her 2 daughters with cancer and in the youngest unaffected daughter. PMID: 26241669
30. 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). PMID: 26391948
31. 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 PMID: 25730140
32. a significant interaction with risk of overall Non Hodgkin lymphoma was observed between WRN rs1346044 and hair dye use before 1980. PMID: 25178586
33. knockdown of WRN reduced TNF-alpha stimulation-induced activation of the endogenous promoter of IL-8, an NF-kappaB-responsive gene, and WRN increased its association with the IL-8 promoter region together with RelA/p50 after TNF-alpha stimulation PMID: 26037922
34. Data indicate that Werner syndrome helicase (WRN)-mediated DNA repair is regulated by SIRT1 deacetylase. PMID: 25801465
35. A nonenzymatic role for WRN in preserving nascent DNA strands following replication stress, is reported. PMID: 25456133
36. our results provide first indication of nonredundant participation of WRN and RECQ1 in protection from potentially carcinogenic effects PMID: 25228686
37. The extent to which heterozygosity at the WRN locus may modify the effect of biallelic SAMHD1 mutations is unknown. PMID: 24989684
38. Data suggest that Werner protein (WRNp) may have a role in controlling autophagy and hereby cellular maintenance. PMID: 25257404
39. The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers. PMID: 24608430
40. Results show increased autophagy in WRN knockdown cells; this was further increased by short-term rapamycin treatment. PMID: 24308646
41. results are consistent with proposed metabolic roles for WRN and genomic instability phenotypes associated with WRN deficiency PMID: 24965941
42. The study demonstrated that helicase/ATPase and exonuclease activities of 4-hydroxy-2-nonenal-modified WRN protein were inhibited both in vitro and in immunocomplexes purified from the cell extracts. PMID: 25170083
43. Using long-term siRNA knockdown of WRN in three ALT cell lines, we show that some, but not all, cell lines require WRN for telomere maintenance. PMID: 24709898
44. WRN and BLM act epistatically with DNA2 to promote the long-range resection of double strand break ends in human cells. PMID: 25122754
45. Werner syndrome protein positively regulates XRCC4-like factor transcription. PMID: 24626809
46. WRN plays a critical role in cancer cell proliferation by contributing to the Warburg effect and preventing metabolic stress. PMID: 24757718
47. Indicate that phosphorylation of Ser-440 and -467 in WRN by DNA-PK is important for relocalization of WRN to nucleoli, and that it is required for efficient DSB repair. PMID: 24429382
48. WRN promoter methylation was associated with irinotecan sensitivity in gastric carcinoma. PMID: 24359226
49. C allele of rs1346044, a non-synonymous SNP resulting in the conversion of Cys to Arg at amino acid position 1367 of WRN, alters susceptibility to ARC, especially the cortical type of the disease, in the Han Chinese. PMID: 23334603
50. A significant interaction of a DNA repair pathway gene WRN and body mass index was observed in T-cell lymphoma. PMID: 23619945

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HGNC: 12791

OMIM: 114500

KEGG: hsa:7486

STRING: 9606.ENSP00000298139

UniGene: Hs.632050