TRF2 overexpression diminishes repair of telomeric single-strand breaks and accelerates telomere shortening in human fibroblasts |
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Authors: | Richter Torsten Saretzki Gabriele Nelson Glyn Melcher Mathias Olijslagers Sharon von Zglinicki Thomas |
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Institution: | Henry Wellcome Biogerontology Laboratory and Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, University of Newcastle upon Tyne, UK. |
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Abstract: | Repair of single strand breaks in telomeric DNA is less efficient than in other genomic regions. This leads to an increased vulnerability of telomeric DNA towards damage induced by reactive oxygen species (ROS) and to accelerated telomere shortening under oxidative stress. The causes for the diminished repair efficacy in telomeres are unknown. We show here that overexpression of the telomere-binding protein TRF2 further reduces telomeric, but not genomic, single strand break repair. This suggests the possibility of strand break repair in telomeres being sterically hindered by the three-dimensional structure of the telomere DNA-protein complex and explains the effect of TRF2 on telomere shortening rates in telomerase-negative cells. |
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Keywords: | Senescence Telomeres TRF2 Reactive oxygen Fibroblast DNA repair Single strand breaks |
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