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Richter, T, Saretzki, G, Nelson, G, Melcher, M, Olijslagers, S and von Zglinicki, T (2007) TRF2 overexpression diminishes repair of telomeric single-strand breaks and accelerates telomere shortening in human fibroblasts. Mech. Ageing Dev. 128:340-5
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.
Cell Line; DNA Breaks, Single-Stranded; DNA Repair/genetics; Fibroblasts/metabolism; Humans; Nuclear Proteins/biosynthesis; Nuclear Proteins/genetics; Nuclear Proteins/physiology; TATA Box Binding Protein-Like Proteins/biosynthesis; TATA Box Binding Protein-Like Proteins/genetics; TATA Box Binding Protein-Like Proteins/physiology; Telomere/genetics; Telomere/metabolism; Telomeric Repeat Binding Protein 2