Analysis of ionizing radiation induced DNA damage response in human adult stem cells and differentiated neurons
- San Antonio, TX (United States)
- Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Findings of neurodegenerative features associated with human radiosensitive syndromes such as Ataxia telangiectasia suggest that DNA repair efficiency is crucial for maintaining the functional integrity of central nervous system. To gain a better understanding of ionizing radiation (IR) induced DNA damage response in undifferentiated and differentiated neural cell types and to evaluate the role of ATM in DNA double strand break (DSB) repair, an in vitro human neural cell differentiation model system was utilized in this study. As compared to adult stem cells, differentiated neurons displayed an attenuated DSB repair response (as judged by the persistence of 53BP1 foci) after IR exposure and the attenuation was even more pronounced in stem cells and neurons after suppression of ATM (Ataxia Telangiectasia Mutated) gene product suggesting the importance of ATM for an optimal DSB repair efficiency in human neural cell types. In corroboration with an attenuated DNA damage response, a sharp decline in the expression levels of several DSB repair genes was observed in neurons. Furthermore, our results suggest that cellular differentiation modulates the expression of several genes thereby compromising the DSB repair fidelity in post mitotic neurons. Further studies are required to verify whether or not ATM mediated exacerbation of DNA repair deficiency in differentiated neurons leads to neurodegeneration.
- Research Organization:
- Columbia Univ., New York, NY (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- Grant/Contract Number:
- FG02-05ER64055
- OSTI ID:
- 1977461
- Alternate ID(s):
- OSTI ID: 1867509
- Journal Information:
- Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Vol. 878, Issue C; ISSN 1383-5718
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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