DNA damage causes ATM-dependent heterochromatin loss leading to nuclear softening, blebbing, and rupture.

The nucleus must maintain stiffness to preserve its shape and integrity to ensure proper function. Defects in nuclear stiffness caused from chromatin and lamin perturbations produce abnormal nuclear shapes common in aging, heart disease, and cancer. Loss of nuclear shape via protrusions called blebs lead to nuclear rupture that is well-established to cause nuclear dysfunction, including DNA damage.