Telomeres resemble double strand DNA breaks (DSBs) and, if not properly packaged and protected, are recognized by the DNA double strand break repair (DSBR) machinery. Initiation of DSB signaling at telomeres due to replicative shortening of telomeres is one of the triggers of cellular senescence, which can also be triggered by other cellular stressors, such as oxidative stress, and oncogenic signaling-induced mitotic arrest. The loss of telomere protection can result in telomere fusions via non-homologous end joining (NHEJ) of microhomology-mediated end joining (MMEJ). Loss of telomere protection accompanied by changes in the organization of telomeric chromatin (O'Sullivan et al. 2014) can trigger extension of telomeres via homologous recombination repair-mediated alternative lengthening of telomeres (ALT). ALT occurs in about 5-15% of cancers and is a telomerase-independent mechanism of replicative immortality. For review, please refer to Arnoult and Karlseder 2015 and Pickett and Reddel 2015.