Cell cycle activation in postmitotic neurons is essential for DNA repair

Increasing evidence indicates that maintenance of neuronal homeostasis involves the activation of the cell cycle machinery in postmitotic neurons. Our recent findings suggest that cell cycle activation is essential for DNA damage-induced neuronal apoptosis. However, whether the cell division cycle also participates in DNA repair and survival of postmitotic, terminally differentiated neurons is unknown. Here, we tested the hypothesis that G ₁ phase components contribute to the repair of DNA and are involved in the DNA damage response of postmitotic neurons. In cortical terminally differentiated neurons, treatment with subtoxic concentrations of hydrogen peroxide (H₂O₂) caused repairable DNA double strand breaks (DSBs) and the activation of G₁ components of the cell cycle machinery. Importantly, DNA repair was attenuated if cyclin-dependent kinases CDK4 and CDK6, essential elements of G₀ → G₁ transition, were suppressed. Our data suggest that G₁ cell cycle components are involved in DNA repair and survival of postmitotic neurons.