DNA damage at Lamina-Associated Domains triggers nuclear envelope reorganization and chromatin detachment to prevent nuclear envelope blebbing and genome instability.

DNA double-strand breaks within lamina-associated domains trigger nuclear lamina remodeling and dynamic detachment of damaged LADs, relocalizing them to the nuclear interior via ATM signaling.

• Why it matters: DNA damage in LADs is poorly understood despite LADs anchoring silent chromatin at the nuclear periphery and supporting genome stability, nuclear architecture, aging, and senescence.
• What they did: Using temporally controlled, spatially precise induction of DSBs within LADs, the study mapped a pathway requiring the ATM/γH2AX/MDC1/RNF168/53BP1 axis and the LINC complex and cytoskeletal components.
• The result: When damaged LADs remain persistently tethered at the periphery, the DNA damage response and repair are delayed, genomic instability increases, and chromatin extrusion through nuclear blebs links failed repair to nuclear integrity dysregulation.