Related Experiment Video
Updated: Aug 26, 2026

Assessing Cell Cycle Progression of Neural Stem and Progenitor Cells in the Mouse Developing Brain after Genotoxic Stress
Published on: May 7, 2014
Cell cycle activation linked to neuronal cell death initiated by DNA damage
Inna I Kruman1, Robert P Wersto, Fernando Cardozo-Pelaez
1Research Resources Branch, Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. inna.kruman@sunhealth.org
Abstract:
Increasing evidence indicates that neurodegeneration involves the activation of the cell cycle machinery in postmitotic neurons. However, the purpose of these cell cycle-associated events in neuronal apoptosis remains unknown. Here we tested the hypothesis that cell cycle activation is a critical component of the DNA damage response in postmitotic neurons. Different genotoxic compounds (etoposide, methotrexate, and homocysteine) induced apoptosis accompanied by cell cycle reentry of terminally differentiated cortical neurons. In contrast, apoptosis initiated by stimuli that do not target DNA (staurosporine and colchicine) did not initiate cell cycle activation. Suppression of the function of ataxia telangiectasia mutated (ATM), a proximal component of DNA damage-induced cell cycle checkpoint pathways, attenuated both apoptosis and cell cycle reentry triggered by DNA damage but did not change the fate of neurons exposed to staurosporine and colchicine. Our data suggest that cell cycle activation is a critical element of the DNA damage response of postmitotic neurons leading to apoptosis.
Insights
Cell cycle activation in neurons signals DNA damage, leading to cell death (apoptosis). Blocking DNA damage response pathways prevents this, but not other cell death triggers.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Neurodegeneration is linked to cell cycle activation in neurons.
- The role of cell cycle events in neuronal apoptosis is unclear.
Purpose of the Study:
- To investigate if cell cycle activation is a key part of the DNA damage response in postmitotic neurons.
- To determine if DNA damage triggers cell cycle reentry and apoptosis.
Main Methods:
- Cortical neurons were treated with genotoxic (etoposide, methotrexate, homocysteine) and non-genotoxic (staurosporine, colchicine) compounds.
- The role of ataxia telangiectasia mutated (ATM) in DNA damage response was assessed.
- Apoptosis and cell cycle reentry were measured.
Main Results:
- Genotoxic compounds induced apoptosis and cell cycle reentry in neurons.
- Non-genotoxic compounds triggered apoptosis without cell cycle activation.
- ATM inhibition reduced DNA damage-induced apoptosis and cell cycle reentry.
Conclusions:
- Cell cycle activation is a critical component of the DNA damage response in postmitotic neurons.
- This response pathway leads to neuronal apoptosis.
- ATM is crucial for mediating DNA damage-induced cell cycle activation and apoptosis.
Related Concept Videos
DNA Damage Can Stall the Cell Cycle
DNA Damage can Stall the Cell Cycle
Inhibition of Cdk Activity
Negative Regulator Molecules
Molecular Factors Affecting Cell Division
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Mitogens and the Cell Cycle

