Figure 1.

Senescence and the DNA damage response. Different stimuli can trigger replicative senescence or stress-induced premature senescence through activation of the DNA damage response. Telomere shortening at each DNA replication or alteration of the shelterin complex (e.g., depletion of TRF2, Telomeric repeat-binding factor 2) leads to the unmasking of chromosomes extremities. Oncogene activation leads to deregulated proliferation, promoting replication errors. Oxidative stresses and various other agents can trigger extensive non-telomeric DNA damage.