OASIS/CREB3L1 is a factor that responds to nuclear envelope stress

Area of Science:

• Cell Biology
• Molecular Biology
• Genomics

Background:

• The nuclear envelope (NE) is crucial for genome stability and chromatin organization.
• Previously considered stable, the NE is now known to be susceptible to damage from various stresses (NE stress).
• NE stress is linked to cellular dysfunction, including genome instability and cell death.

Purpose of the Study:

• To investigate the role of the endoplasmic reticulum (ER)-resident transmembrane transcription factor OASIS in response to NE stress.
• To elucidate the molecular mechanisms underlying NE stress response pathways.

Main Methods:

• Investigated the localization of OASIS in response to NE stress.
• Analyzed the interaction of OASIS with nuclear lamina components and cytoskeletal complexes.
• Assessed the functional impact of OASIS on DNA damage and nuclear deformation under NE stress.

Main Results:

• OASIS accumulates in its full-length form at damaged NE sites, distinct from its response to ER stress.
• Lamin proteins are depleted where OASIS accumulates, and OASIS specifically localizes to damaged NE.
• OASIS colocalizes with components of the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex (SUN2, Nesprin-2) and NE repair factors (BAF, LEM, ESCRT III).
• OASIS mitigates DNA damage and nuclear deformation caused by NE stress.

Conclusions:

• OASIS is a key mediator of a novel NE stress response pathway.
• OASIS accumulation at damaged NE sites is a specific response to NE stress, not ER stress.
• OASIS actively participates in NE repair and genome protection under stress conditions.