A three-state model of telomere control over human proliferative boundaries

► Human telomeres are protected from the DDR by a higher-order structure. ► Intermediate-state telomeres are susceptible to a DDR and regulate senescence. ► Uncapped-state telomeres are susceptible to fusions and induce crisis. ► Intermediate-state telomeres regulate the prolonged mitosis checkpoint. ► Telomeres may serve as epigenetic sensors of cellular stress.