Cell cycle activation in postmitotic neurons is essential for DNA repair

Elena I. Schwartz, Lubomir B. Smilenov, Mary A. Price, Tracy Osredkar, Ronald A. Baker, Soma Ghosh, Fu Dong Shi, Timothy L. Vollmer, Alejandro Lencinas, Diane M. Stearns, Myriam Gorospe, Inna I. Kruman

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)318-329
Number of pages12
JournalCell Cycle
Volume6
Issue number3
DOIs
StatePublished - Feb 1 2007

Keywords

  • Apoptosis
  • Cell cycle
  • DNA damage
  • DNA repair
  • Neuron

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Schwartz, E. I., Smilenov, L. B., Price, M. A., Osredkar, T., Baker, R. A., Ghosh, S., Shi, F. D., Vollmer, T. L., Lencinas, A., Stearns, D. M., Gorospe, M., & Kruman, I. I. (2007). Cell cycle activation in postmitotic neurons is essential for DNA repair. Cell Cycle, 6(3), 318-329. https://doi.org/10.4161/cc.6.3.3752