RT Journal Article
SR Electronic
T1 Defective Telomere Lagging Strand Synthesis in Cells Lacking WRN Helicase Activity
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1951
OP 1953
DO 10.1126/science.1103619
VO 306
IS 5703
A1 Crabbe, Laure
A1 Verdun, Ramiro E.
A1 Haggblom, Candy I.
A1 Karlseder, Jan
YR 2004
UL http://science.sciencemag.org/content/306/5703/1951.abstract
AB 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.