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

ABSTRACT: 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. However, it remains unknown how increased DNA damage affects nuclear stiffness, shape, and ruptures, which could create a feedback loop. To determine whether increased DNA damage alters nuclear physical properties, we treated mouse embryonic fibroblast cells with DNA damage drugs cisplatin and bleomycin. DNA damage drugs caused increased nuclear blebbing and rupture in interphase nuclei within a

SUBMITTER: Eskndir N 

PROVIDER: S-EPMC11974953 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature