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The premature ageing syndrome protein, WRN, is a 3′→5′ exonuclease

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

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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.

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Figure 1: Exonuclease activity of wild-type WRN and the N333 fragment.
Figure 2: Helicase and exonuclease activities of wild-type and mutant WRN proteins.

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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.

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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

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  1. Shurong Huang
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Correspondence to Judith Campisi.

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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

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