Modulation of DNA base excision repair during neuronal differentiation

NEUROBIOLOGY OF AGING

卷:34

Article

Sykora, Peter¹  Yang, Jenq-Lin^1,2  Ferrarelli, Leslie K.¹  Tian, Jingyan¹  Tadokoro, Takashi¹  Kulkarni, Avanti³  Weissman, Lior¹  Keijzers, Guido^1,4  Wilson, David M., III¹  Mattson, Mark P.²  Bohr, Vilhelm A.¹ 

[1] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA

[2] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA

[3] Roche Palo Alto LLC, Palo Alto, CA USA

[4] Univ Copenhagen, Ctr Hlth Aging, Fac Hlth Sci, DK-1168 Copenhagen, Denmark

关键词: BER;    Differentiation;    DNA repair;    Postmitotic;    Aging;    Neuron;    DNA damage;   

DOI  :  10.1016/j.neurobiolaging.2012.12.016

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free