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Gene Review

Wrn  -  Werner syndrome homolog (human)

Mus musculus

Synonyms: AI846146, Exonuclease WRN, Werner syndrome ATP-dependent helicase homolog
 
 
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Disease relevance of Wrn

 

High impact information on Wrn

  • These genetic data indicate that the delayed manifestation of the complex pleiotropic of Wrn deficiency relates to telomere shortening [1].
  • So, the impact on gene expression profile when both Wrn and PARP-1 are mutated was greater than a simple addition of individual mutant genotype [3].
  • In contrast, the p53 null/Wrn mutant mice were particularly remarkable with respect to the rapidity with which they developed tumors [4].
  • Further, we strengthen this notion by introducing an inactivating mutation in the murine Wrn gene (a gene important in maintenance of genome stability) and showing that bigenic Tg.AC/Wrn(Deltahel/Deltahel) mice experience an eightfold increase in inactivating germline mutations at the Tg.AC locus [2].
  • Our results suggest that Wrn, Blm, and RecQ1 are not involved in sequence-specific mRNA degradation in mammals in response to dsRNA, suggesting potential differences in the mammalian RNAi pathway [5].
 

Biological context of Wrn

 

Other interactions of Wrn

  • Interestingly, more than 58% of misregulated genes identified in double mutant cells were not altered in cells with either the Wrn or PARP-1 mutation alone [3].

References

  1. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Chang, S., Multani, A.S., Cabrera, N.G., Naylor, M.L., Laud, P., Lombard, D., Pathak, S., Guarente, L., DePinho, R.A. Nat. Genet. (2004) [Pubmed]
  2. Genetic interaction between the unstable v-Ha-RAS transgene (Tg.AC) and the murine Werner syndrome gene: transgene instability and tumorigenesis. Leder, A., Lebel, M., Zhou, F., Fontaine, K., Bishop, A., Leder, P. Oncogene (2002) [Pubmed]
  3. In vivo misregulation of genes involved in apoptosis, development and oxidative stress in mice lacking both functional Werner syndrome protein and poly(ADP-ribose) polymerase-1. Deschênes, F., Massip, L., Garand, C., Lebel, M. Hum. Mol. Genet. (2005) [Pubmed]
  4. Tumorigenic effect of nonfunctional p53 or p21 in mice mutant in the Werner syndrome helicase. Lebel, M., Cardiff, R.D., Leder, P. Cancer Res. (2001) [Pubmed]
  5. Analysis of the role of RecQ helicases in RNAi in mammals. Stein, P., Svoboda, P., Stumpo, D.J., Blackshear, P.J., Lombard, D.B., Johnson, B., Schultz, R.M. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  6. Increased frequency of multiradial chromosome structures in mouse embryonic fibroblasts lacking functional Werner syndrome protein and poly(ADP-ribose) polymerase-1. Lavoie, J., Carter, R., Drouin, R., Lebel, M. Cancer Genet. Cytogenet. (2005) [Pubmed]
 
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