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The caspase-activated DNase promotes cellular senescence
Aladin Haimovici1, Valentin Rupp2, Tarek Amer2
1Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Faculty of Medicine, Freiburg, Germany. aladin.haimovici@uniklinik-freiburg.de.
The EMBO Journal
|July 8, 2024
Summary
The caspase-activated DNase (CAD) enzyme initiates cellular senescence by causing DNA damage, even without cell death. This discovery reveals CAD as a key factor in senescence across various stress responses.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Cellular senescence is a stress response characterized by DNA damage, but its origins are often unclear.
- The enzyme caspase-activated DNase (CAD) is known to degrade DNA during apoptosis.
Purpose of the Study:
- To identify the source of DNA damage in cellular senescence.
- To investigate the role of CAD in initiating senescence.
Main Methods:
- Investigated CAD activation by sub-lethal apoptotic signals.
- Assessed senescence induction by oncogenic RAS, type-I interferon, and doxorubicin.
- Experimentally activated CAD in human cells.
- Studied senescence in CAD-deficient mice.
Main Results:
- Sub-lethal apoptotic signals activate CAD, causing DNA damage and senescence without cell death.
- CAD is essential for senescence induced by oncogenic RAS, type-I interferon, and doxorubicin.
- Direct CAD activation is sufficient to induce senescence in human cells.
- CAD-deficient mice show reduced senescence in aging organs.
Conclusions:
- CAD-induced DNA damage is a critical mechanism for initiating cellular senescence.
- CAD acts as a central mediator of senescence in response to diverse cellular insults.
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