Figure 4

Model for amplification of chromosomal instability by DNA damage. Initial merotelic attachments activate DNA damage signaling and inhibit cell proliferation through anaphase delay and induction of apoptosis or senescence. To overcome the block, the downstream spindle checkpoint is suppressed in CIN tumors, increasing the frequency of spindle attachment errors. As a side effect of this continuous breakage, DNA repair mechanisms remain activated, leading ultimately to adaptation through suppression of apoptosis and senescence and through spindle checkpoint relaxation (dashed lines).