The premature ageing syndrome protein, WRN, is a 3′→5′ exonuclease (original) (raw)

Nature Genetics volume 20, pages 114–116 (1998)Cite this article

Werner syndrome (WS) is a human autosomal recessive disorder that causes the premature appearance of a partial array of disorders characteristic of old age1,2. These disorders include atherosclerosis, cancer, type 2 diabetes, osteoporosis, cataracts, wrinkled skin and grey hair, among other ailments. Cells cultured from WS subjects have a shortened replicative life span3,4 and elevated rates of chromosome translocations, large deletions and homologous recombination5,6. The gene defective in WS, WRN, encodes a large RecQ-like DNA helicase7 of 1432 aa. Defects in another human RecQ-like helicase, BLM, result in Bloom's syndrome8 (BS), a genetic disorder that is quite different from WS. BS is manifested by short stature, neoplasia, immunodeficiency and high risk of cancer. Cells from BS subjects show an increase in sister chromatid exchanges.

DNA helicases can function in replication, repair, recombination, transcription or RNA processing. As WRN and BLM share no obvious homology outside the helicase domain, the non-helicase domains probably determine in which process each RecQ-like helicase participates, which provides the basis for the disparate cellular and organismal phenotypes that result from defects in these proteins.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

References

  1. Martin, G.M. Birth Defects 14, 5–39 ( 1978).
    CAS PubMed Google Scholar
  2. Goto, M. Mech. Ageing Dev. 98, 239–254 (1997).
    Article CAS Google Scholar
  3. Martin, G.M., Sprague, C.A. & Epstein, C.J. Lab. Invest. 23, 86– 92 (1970).
    CAS PubMed Google Scholar
  4. Salk, D., Bryant, E., Hoehn, H., Johnston, P. & Martin, G.M. Adv. Exp. Bio. Med. 190, 305–311 (1985).
    Article CAS Google Scholar
  5. Fukuchi, K., Martin, G.M. & Monnat, R.J. Proc. Natl Acad. Sci. USA 86, 5893–5897 (1989).
    Article CAS Google Scholar
  6. Cheng, R.Z., Murano, S., Kurz, B. & Shmookler-Reis, R.J. Mutat. Res. 237, 259–269 ( 1990).
    Article CAS Google Scholar
  7. Yu, C.E. et al. Science 272, 258–262 (1996).
    Article CAS Google Scholar
  8. German, J. Medicine 72, 393–406 ( 1993).
    Article CAS Google Scholar
  9. Main, I.S. Nucleic Acids Res. 25, 3187–3195 (1997).
    Article Google Scholar
  10. Mushegian, A.R., Bassett, D.E. Jr, Boguski, M.S., Bork, P., & Koonin, E.V. Proc. Natl Acad. Sci. USA 94, 5831–5836 ( 1997).
    Article CAS Google Scholar
  11. Gray, M.D. et al. Nature Genet. 17, 100– 103 (1997).
    Article CAS Google Scholar
  12. Linn, S.M., Lloyd, R.S. & Roberts, R.T. Nucleases (Cold Spring Harbor Laboratory Press, New York, 1993).
  13. Yamagata, K. et al. Proc. Natl Acad. Sci. USA 95, 8733– 8738 (1998).
    Article CAS Google Scholar
  14. Ogburn, C.E. et al. Hum. Genet. 101, 121– 125 (1997).
    Article CAS Google Scholar
  15. Yan, H., Chen, C.-Y., Kobayashi, R. & Newport, J. Nature Genet. 19, 375–378 (1998).
    Article CAS Google Scholar

Download references

Acknowledgements

We thank S. Linn for valuable discussions and H. Asahara for technical advice. This work was supported by the National Institute on Ageing (grants AG11658 (J.C.); AG05776 (S.H.); AG14446 (J.O.)) and Department of Energy under contract DE-AC0376SF00098 to the University of California.

Author information

Authors and Affiliations

  1. Department of Cell and Molecular Biology, Lawrence Berkeley National Laboratory, Berkeley, 94720, California, USA
    Shurong Huang, Baomin Li & Judith Campisi
  2. Department of Pathology, University of Washington, Seattle, 98195, Washington, USA
    Matthew D. Gray & Junko Oshima
  3. Department of Radiation Biology, Lawrence Berkeley National Laboratory, Berkeley, 94720, California, USA
    I. Saira Mian

Authors

  1. Shurong Huang
    You can also search for this author inPubMed Google Scholar
  2. Baomin Li
    You can also search for this author inPubMed Google Scholar
  3. Matthew D. Gray
    You can also search for this author inPubMed Google Scholar
  4. Junko Oshima
    You can also search for this author inPubMed Google Scholar
  5. I. Saira Mian
    You can also search for this author inPubMed Google Scholar
  6. Judith Campisi
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toJudith Campisi.

Rights and permissions

About this article

Cite this article

Huang, S., Li, B., Gray, M. et al. The premature ageing syndrome protein, WRN, is a 3′→5′ exonuclease.Nat Genet 20, 114–116 (1998). https://doi.org/10.1038/2410

Download citation