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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 and Inna I. Kruman
volume 6 | issue 3
1 February 2007Pages: 318 - 329
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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 G1 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.
Authors
Elena I. Schwartz
Georgetown University Medical Center; Washing DC, USA
Lubomir B. Smilenov
Columbia University; New York, NY USA
Mary A. Price
Barrow Neurological Institute; Phoenix, AZ USA
Tracy Osredkar
Sun Health Research Institute; Sun City, AZ USA
Ronald A. Baker
Columbia University; New York, NY USA
Soma Ghosh
NICHD, NIH; Bethesda, MD USA
Fu-Dong Shi
Barrow Neurological Institute; Phoenix, AZ USA
Timothy L. Vollmer
Barrow Neurological Institute; Phoenix, AZ USA
Alejandro Lencinas
NAU; Flagstaff, AZ USA
Diane M. Stearns
NAU; Flagstaff, AZ USA
Myriam Gorospe
National Institutes of Health; Baltimore, MD
Inna I. Kruman
Sun Health Research Institute; Sun City, AZ USA
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.