What this means
The nuclear periphery anchors large, transcriptionally silent chromatin domains to the nuclear envelope and plays a central role in maintaining genome stability, acting as a dynamic hub for DNA repair. Nevertheless, how cells process DNA damage within lamina-associated domains (LADs), which reside in this environment, remains poorly understood, despite their relevance to nuclear architecture, aging, and senescence.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- Not stated
- Kind of research
- Early results, not yet checked by other scientists
The science
- Original title
- DNA damage at Lamina-Associated Domains triggers nuclear envelope reorganization and chromatin detachment to prevent nuclear envelope blebbing and genome instability.
- Authors
- Rubio-Contreras, D., Audibert, S., Fernandez, J. et al.
- Journal
- bioRxiv (preprint, not yet peer reviewed)
- Published
- Oct 27, 2026
- Study type
- Preprint
Abstract
The nuclear periphery anchors large, transcriptionally silent chromatin domains to the nuclear envelope and plays a central role in maintaining genome stability, acting as a dynamic hub for DNA repair. Nevertheless, how cells process DNA damage within lamina-associated domains (LADs), which reside in this environment, remains poorly understood, despite their relevance to nuclear architecture, aging, and senescence. By employing systems for temporally controlled and spatially precise induction of DNA double-strand breaks (DSBs) within LADs, we show that DSBs within LADs trigger remodeling of the nuclear lamina and the dynamic detachment of damaged LADs from the nuclear envelope, resulting in their relocalization to the nuclear interior. This process is orchestrated by the ATM/{gamma}H2AX/MDC1/RNF168/53BP1 axis and requires the linker of nucleoskeleton and cytoskeleton (LINC) complex and cytoskeletal components while leaving DNA repair pathway choice unchanged. Persistent tethering of damaged LADs at the nuclear periphery delays the DNA damage response and repair, elevates genomic instability, and drives chromatin extrusion through nuclear blebs directly linking failed repair to dysregulation of nuclear integrity. These findings reveal a protective mechanism in which ATM-driven LAD dynamics and nuclear envelope remodeling might relieve mechanical stress, facilitate repair, and safeguard both genome stability and nuclear architecture.
Rubio-Contreras, D., Audibert, S., Fernandez, J. et al. DNA damage at Lamina-Associated Domains triggers nuclear envelope reorganization and chromatin detachment to prevent nuclear envelope blebbing and genome instability. bioRxiv. 2026. doi:10.64898/2026.10.25.761546. https://doi.org/10.64898/2026.10.25.761546