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The three faces of the WS helicase

Nature Genetics volume 19, pages 308–309 (1998)Cite this article

Janus, the guardian god of portals and the patron of beginnings and endings, has two faces, one facing forward and the other, backward. Going one up on him, WRN — the DNA helicase defective in Werner syndrome (WS) patients — appears to have at least three different faces when it comes to function. WS is a rare, recessively inherited disease characterized by premature ageing. Individuals with WS develop normally until puberty, when they manifest accelerated atherosclerosis, osteoporosis and a higher incidence of diabetes1. They also have an elevated risk of several different types of tumours2. Cells cultured from WS patients have a short replicative lifespan and increased genetic instability which is manifested at the cytogenetic level by chromosome breaks and translocations, and at the molecular level by multiple large DNA deletions3. An unexpected observation is now documented by Hong Yan and colleagues4, who have identified the Xenopus laevis orthologue of WRN and demonstrated its essential role in the formation of replication foci.

WRN has a central domain containing seven helicase sequence motifs common to all DNA helicases5. It shares homology with the RecQ family of DNA helicases, which include Escherichia coli RecQ, Saccharomyces cerevisiae Sgs-1p, Schizosaccharomyces pombe Rqh-1p and the human RecQL and BLM proteins. Furthermore, expression studies in insect cells have revealed that WRN has an ATP-dependent 3´→5´ DNA-unwinding activity, thus establishing it as a bona fide DNA helicase6. It is, however, distinct from other members of the RecQ family in that it bears an amino-terminal domain with significant similarity to the 3´→5´ proofreading domain of E. coli DNA polymerase I, with RNaseD, and with the nuclease domain of polymyositis/scleroderma nuclear autoantigen7,8.

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Authors and Affiliations

  1. Unit of Biochemistry, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 31096, Israel

    Michael Fry

  2. Department of Pathology, Gottstein Cancer Research Laboratory, University of Washington, Seattle, 98195 - 7705, Washington, USA

    Lawrence A Loeb

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  1. Michael Fry
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  2. Lawrence A Loeb
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Fry, M., Loeb, L. The three faces of the WS helicase. Nat Genet 19, 308–309 (1998). https://doi.org/10.1038/1188

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