Figure 4.

Impact of oxidative stress on telomeres and telomere-associated proteins in mammals. Telomeres are a hot spot for oxidative damage causing base modifications including thymine to thymine glycol and guanine to 8-oxoG. These lesions interfere with DNA binding by TRF1, TRF2, and POT1. These same proteins stimulate BER at telomeres and perhaps elsewhere in the genome, enabling the removal of damaged bases from the DNA. Oxidative DNA damage decreases the abundance of both cytoplasmic and nuclear RAP1, which in turn triggers apoptosis. Conversely, oxidative stress leads to the accumulation in mitochondria of TERT and TIN2, which promote mitochondrial functions that protect against apoptosis.