Camptothecin sensitivity in Werner syndrome fibroblasts as assessed by the COMET technique

Lowe, J.E., Sheerin, Angela, Jennert-Burston, Katrin, Burton, D., Ostler, Elizabeth, Bird, J., Green, M.H.L. and Faragher, Richard (2004) Camptothecin sensitivity in Werner syndrome fibroblasts as assessed by the COMET technique Annals of the New York Academy of Sciences, 1019. pp. 256-259. ISSN 1749-6632

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Werner syndrome (WS) is an inherited genetic disease in which individuals display the premature aging of a selected subset of tissues. The disorder results from the loss of function mutations in the wrn gene. Wrn codes for a member of the RecQ helicase family with a unique nuclease domain. There is significant evidence that the role of wrn is to assist in the repair and reinitiation of DNA replication forks that have stalled. Loss of the wrn helicase imposes a distinct set of phenotypes at the cellular level. These include premature replicative senescence (in a subset of cell types), chromosomal instability, a distinct mutator phenotype, and hypersensitivity to a limited number of DNA damaging agents. Unfortunately, most of these phenotypes are not suitable for the rapid assessment of loss of function of the wrn gene product. However, WS cells have been reported to show abnormal sensitivity to the drug camptothecin (an inhibitor of topoisomerase type I). A rapid assay for this sensitivity would be a useful marker of loss of wrn function. The COMET (single-cell gel electrophoresis) assay is a rapid, sensitive, versatile, and robust technique for the quantitative assessment of DNA damage in eukaryotic cells. Using this assay, we have found that a significantly increased level of strand breaks can be demonstrated in WS cells treated with camptothecin compared with normal controls.

Item Type: Journal article
Uncontrolled Keywords: replicative senescence; Werner syndrome; COMET assay; camptothecin
Subjects: B000 Health Professions > B100 Anatomy Physiology and Pathology
DOI (a stable link to the resource): 10.1196/annals.1297.042
Faculties: Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences
Depositing User: editor spbs
Date Deposited: 20 Dec 2007
Last Modified: 18 Mar 2015 11:42

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