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Updated: Aug 6, 2025
Planarian Immobilization, Partial Irradiation, and Tissue Transplantation
Published on: August 6, 2012
Inhibition of ATM kinase rescues planarian regeneration after lethal radiation
Divya A Shiroor1, Kuang-Tse Wang1, Bhargav D Sanketi1
1Department of Molecular Medicine, Cornell University College of Veterinary Medicine, Ithaca, NY, USA.
Abstract:
As stem cells divide, they acquire mutations that can be passed on to daughter cells. To mitigate potentially deleterious outcomes, cells activate the DNA damage response (DDR) network, which governs several cellular outcomes following DNA damage, including repairing DNA or undergoing apoptosis. At the helm of the DDR are three PI3-like kinases including Ataxia-Telangiectasia Mutated (ATM). We report here that knockdown of ATM in planarian flatworms enables stem cells to withstand lethal doses of radiation which would otherwise induce cell death. In this context, stem cells circumvent apoptosis, replicate their DNA, and recover function using homologous recombination-mediated DNA repair. Despite radiation exposure, atm knockdown animals survive long-term and regenerate new tissues. These effects occur independently of ATM's canonical downstream effector p53. Together, our results demonstrate that in planarians, ATM promotes radiation-induced apoptosis. This acute, ATM-dependent apoptosis is a key determinant of long-term animal survival. Our results suggest that inhibition of ATM in these organisms could, therefore, potentially favor cell survival after radiation without obvious effects on stem cell behavior.
Insights
In planarian flatworms, inhibiting Ataxia-Telangiectasia Mutated (ATM) kinase allows stem cells to survive lethal radiation doses. This survival is linked to DNA repair and regeneration, independent of p53.
Area of Science:
- Cellular Biology
- Genetics
- Regenerative Medicine
Background:
- Stem cell division can lead to mutations.
- The DNA damage response (DDR) network, involving kinases like ATM, regulates cellular outcomes after DNA damage.
- ATM plays a role in DNA repair and apoptosis.
Purpose of the Study:
- To investigate the role of ATM in radiation response and stem cell survival in planarian flatworms.
- To determine if inhibiting ATM affects stem cell behavior and long-term survival after radiation exposure.
Main Methods:
- Knockdown of ATM in planarian flatworms.
- Exposure of planarians to lethal doses of radiation.
- Assessment of stem cell survival, DNA repair mechanisms (homologous recombination), and animal regeneration.
- Analysis of the role of p53 in ATM-mediated radiation response.
Main Results:
- ATM knockdown enabled planarian stem cells to survive lethal radiation doses.
- Stem cells in atm knockdown planarians underwent DNA replication and functional recovery via homologous recombination.
- atm knockdown planarians survived long-term and regenerated tissues despite radiation exposure.
- These effects were independent of ATM's known downstream effector, p53.
- ATM was found to promote radiation-induced apoptosis in planarians, which is crucial for long-term survival.
Conclusions:
- ATM promotes apoptosis following radiation exposure in planarians, and this process is essential for long-term animal survival.
- Inhibiting ATM in planarians can enhance stem cell survival after radiation without apparent negative effects on stem cell behavior or regeneration.
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