期刊
NEUROBIOLOGY OF AGING
卷 34, 期 7, 页码 1717-1727出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2012.12.016
关键词
BER; Differentiation; DNA repair; Postmitotic; Aging; Neuron; DNA damage
资金
- National Institute on Aging, National Institutes of Health
Neurons are terminally differentiated cells with a high rate of metabolism and multiple biological properties distinct from their undifferentiated precursors. Previous studies showed that nucleotide excision DNA repair is downregulated in postmitotic muscle cells and neurons. Here, we characterize DNA damage susceptibility and base excision DNA repair (BER) capacity in undifferentiated and differentiated human neural cells. The results show that undifferentiated human SH-SY5Y neuroblastoma cells are less sensitive to oxidative damage than their differentiated counterparts, in part because they have robust BER capacity, which is heavily attenuated in postmitotic neurons. The reduction in BER activity in differentiated cells correlates with diminished protein levels of key long patch BER components, flap endonuclease-1, proliferating cell nuclear antigen, and ligase I. Thus, because of their higher BER capacity, proliferative neural progenitor cells are more efficient at repairing DNA damage compared with their neuronally differentiated progeny. Published by Elsevier Inc.
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