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Science 10 December 2004:
Vol. 306. no. 5703, pp. 1951 - 1953
DOI: 10.1126/science.1103619
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Reports

Defective Telomere Lagging Strand Synthesis in Cells Lacking WRN Helicase Activity

Laure Crabbe, Ramiro E. Verdun, Candy I. Haggblom, Jan Karlseder*

Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening rates, and genome instability. The syndrome is caused by the loss of the RecQ helicase WRN, but the underlying molecular mechanism is unclear. Here we report that cells lacking WRN exhibit deletion of telomeres from single sister chromatids. Only telomeres replicated by lagging strand synthesis were affected, and prevention of loss of individual telomeres was dependent on the helicase activity of WRN. Telomere loss could be counteracted by telomerase activity. We propose that WRN is necessary for efficient replication of G-rich telomeric DNA, preventing telomere dysfunction and consequent genomic instability.

The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.

* To whom correspondence should be addressed. E-mail: Karlseder{at}salk.edu

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