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Title: Defective Artemis causes mild telomere dysfunction
Authors: Yasaei, H
Slijepcevic, P
Keywords: Telomere;DNA damage response;Artemis;Ionizing radiation
Issue Date: 2010
Publisher: BioMed Central
Citation: Genome Integrity. 1:3
Abstract: Background: Repair of DNA double strand breaks by non-homologous end joining (NHEJ) requires several proteins including Ku, DNA-PKcs, Artemis, XRCC4, Ligase IV and XLF. Two of these proteins, namely Ku and DNA-PKcs, are also involved in maintenance of telomeres, chromosome end-structures. In contrast, cells defective in Ligase IV and XRCC4 do not show changes in telomere length or function suggesting that these proteins are not involved in telomere maintenance. Since a mouse study indicated that defective Artemis may cause telomere dysfunction we investigated the effects of defective Artemis on telomere maintenance in human cells. Results: We observed significantly elevated frequencies of telomeric fusions in two primary fibroblast cell lines established from Artemis defective patients relative to the control cell line. The frequencies of telomeric fusions increased after exposure of Artemis defective cells to ionizing radiation. Furthermore, we observed increased incidence of DNA damage at telomeres in Artemis defective cells that underwent more than 32 population doublings using the TIF (Telomere dysfunction Induced Foci) assay. We have also inhibited the expression levels of DNA-PKcs in Artemis defective cell lines by either using synthetic inhibitor (IC86621) or RNAi and observed their greater sensitivity to telomere dysfunction relative to control cells. Conclusion: These results suggest that defective Artemis causes a mild telomere dysfunction phenotype in human cell lines.
Description: This article has been made available through the Brunel Open Access Publishing Fund.
Appears in Collections:Biological Sciences
Brunel OA Publishing Fund
Dept of Life Sciences Research Papers

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