OrganismHomo sapiens
Aging PhenotypeShortened life-span
Allele TypeRecessive
DescriptionMutation of WRN causes Werner Syndrome. The features of Werner syndrome include prematurely aged facies, scleroderma-like skin changes, cataracts, arteriosclerosis, subcutaneous calcification, and diabetes mellitus (McKusick et al, 1963; Epstein et al, 1966). Inheritance is autosomal recessive. Malignancy is frequent. The frequency is 3 per million persons in Japan (Goto et al, 1981).
Gene FunctionPositional cloning led to the identification of the WRN gene, which codes for DNA helicase, with an exonuclease domain as well (Yu et al, 1996). The subcellular localization of WRN is primary nucleolar (Marciniak et al, 1998). WRN has 3’ tp 5’ exonuclease activity (Huang et al., 1998)
Other PhenotypesCells from a Werner heterozygote exit the cell cycle at a faster rate than do normal cells (Faragher et al, 1993). Loss of WRN promotes aberrant mitotic recombination (Prince et al., 2001).
HomologsS.c. SGS1
S.p. rqh1
C.e. TO4A11.6, E03A3.2
D.m. blm, recq5, recq4,
R.n. RN3436, RN14550
M.m. Wrn, MM.27407, Blm,
Primary ReferenceMcKusick, V. A.; Abbey, H.; Bartalos, M.; Bowen, P.; Boyer, S. H., IV; Cohen, B. H.; Danks, D. M.; Duchastel, Y.; Emery, A. E. H.; Epstein, E. J.; Fainer, D. C.; Finn, R.; and 18 others (1963). Medical genetics 1962. J. Chronic Dis. 16, 457-634.
Other ReferencesEpstein, C. J.; Martin, G. M.; Schultz, A. L.; Motulsky, A. G. (1966). Werner's syndrome: a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine 45, 177-222.
Faragher, R. G. A.; Kill, I. R.; Hunter, J. A. A.; Pope, F. M.; Tannock, C.; Shall, S. (1993). The gene responsible for Werner syndrome may be a cell division 'counting' gene. Proc. Nat. Acad. Sci. 90, 12030-12034. [Abstract]
Goto, M.; Tanimoto, K.; Horiuchi, Y.; Sasazuki, T. (1981) Family analysis of Werner's syndrome: a survey of 42 Japanese families with a review of the literature. Clin. Genet. 19, 8-15. [Abstract]
Huang, S., Li, B., Gray, M. D., Oshima, J., Mian, I. S., and Campisi, J. (1998). The premature ageing syndrome protein, WRN, is a 3'-->5' exonuclease. Nat Genet 20, 114-6. [Abstract]
Prince, P. R., Emond, M. J., and Monnat, R. J., Jr. (2001). Loss of Werner syndrome protein function promotes aberrant mitotic recombination. Genes Dev 15, 933-8. [Abstract]
Yu, C.E.; Oshima, J.; Fu, Y.-H.; Wijsman, E. M.; Hisama, F.; Alisch, R.; Matthews, S.; Nakura, J.; Miki, T.; Quais, S.; Martin, G. M.; Mulligan, J.;
Schellenberg, G. D. (1996). Positional cloning of the Werner's syndrome gene. Science 272, 258-262. [Abstract]
Relevant LinksUW
KeywordsHomo, sapiens, human, nucleolus, DNA damage, recombination, cancer, replicative senescence, telomeres, DNA, cell cycle, Werner Syndrome, progeria