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ssDNA fragments induce cell senescence by telomere uncapping

Lookup NU author(s): Avgi Tsolou, Dr Joao Passos, Dr Glyn Nelson, Dr Yasumichi Arai, Professor Thomas von Zglinicki

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Abstract

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.


Publication metadata

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


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