Related Experiment Video
Updated: Mar 2, 2026

Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
cGAS is essential for cellular senescence
Hui Yang1,2, Hanze Wang3, Junyao Ren1,2
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148.
Abstract:
Cellular senescence is a natural barrier to tumorigenesis and it contributes to the antitumor effects of several therapies, including radiation and chemotherapeutic drugs. Senescence also plays an important role in aging, fibrosis, and tissue repair. The DNA damage response is a key event leading to senescence, which is characterized by the senescence-associated secretory phenotype (SASP) that includes expression of inflammatory cytokines. Here we show that cGMP-AMP (cGAMP) synthase (cGAS), a cytosolic DNA sensor that activates innate immunity, is essential for senescence. Deletion of cGAS accelerated the spontaneous immortalization of mouse embryonic fibroblasts. cGAS deletion also abrogated SASP induced by spontaneous immortalization or DNA damaging agents, including radiation and etoposide. cGAS is localized in the cytoplasm of nondividing cells but enters the nucleus and associates with chromatin DNA during mitosis in proliferating cells. DNA damage leads to accumulation of damaged DNA in cytoplasmic foci that contain cGAS. In human lung adenocarcinoma patients, low expression of cGAS is correlated with poor survival. These results indicate that cGAS mediates cellular senescence and retards immortalization. This is distinct from, and complementary to, the role of cGAS in activating antitumor immunity.
Related Concept Videos
Replicative Cell Senescence
Caspases
Inhibition of Cdk Activity
Negative Regulator Molecules
The Cell Cycle Control System
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
Cell Specific Gene Expression

