Skip to Content
Merck
  • Inhibition of ATM kinase rescues planarian regeneration after lethal radiation.

Inhibition of ATM kinase rescues planarian regeneration after lethal radiation.

EMBO reports (2023-03-22)
Divya A Shiroor, Kuang-Tse Wang, Bhargav D Sanketi, Justin K Tapper, Carolyn E Adler
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-phospho Histone H3 S10 Antibody, clone 63-1C-8 , ZooMAb® Rabbit Monoclonal, recombinant, expressed in HEK 293 cells
Roche
Anti-Digoxigenin-POD, Fab fragments, from sheep
Roche
Anti-Fluorescein-POD, Fab fragments, from sheep
Roche
Anti-Digoxigenin-AP, Fab fragments, from sheep