Browse by author
Lookup NU author(s): Avgi Tsolou, Dr Joao Passos, Dr Glyn NelsonORCiD, Dr Yasumichi Arai, Professor Thomas von Zglinicki
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Telomere uncapping is known to induce senescence by activating a DNA damage response (DDR). However, it is still unclear what structural features of uncapped telomeres activate DDR. One hypothesis is that the exposure of the telomeric single-stranded G-rich 3' overhang triggers a DNA damage response and is, thus, equivalent to telomere uncapping. To mimic this, we compared the effects of two short single-stranded oligonucleotides, (TTAGGG)(2) and (CCCTAA)(2). G-rich oligonucleotides induced DNA damage foci containing gamma H2AX and senescence-like arrest, whilst C-rich oligonucleotides had no effect. Oligonucleotides did not co-localize with gamma H2AX foci, instead the induced DNA damage foci were preferentially localized at telomeres. BrdU incorporation assays showed that the effect of G oligonucleotides on gamma H2AX foci formation was cell cycle-dependent; entry of cells into S phase was necessary for subsequent DNA damage foci formation. Together, our results show that short G-rich single-stranded oligonucleotides induce telomere uncapping in a cell cycle-dependent manner, probably by titrating essential factors like Pot1 away from telomeres. (C) 2008 Elsevier Inc. All rights reserved.
Author(s): Tsolou A, Passos JF, Nelson G, Arai Y, von Zglinicki T
Publication type: Article
Publication status: Published
Journal: Experimental Gerontology
Year: 2008
Volume: 43
Issue: 10
Pages: 892-899
ISSN (print): 0531-5565
ISSN (electronic): 1873-6815
Publisher: Elsevier Inc.
URL: http://dx.doi.org/10.1016/j.exger.2008.08.043
DOI: 10.1016/j.exger.2008.08.043
Altmetrics provided by Altmetric
