title: Modulation of DNA base excision repair during neuronal differentiation.
abstract: 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.
authors: Laboratory of Molecular Gerontology, National Institute on Aging/National Institutes of Health, Baltimore, MD, USA.
authors: Peter
authors: P
authors: Sykora
authors: Jenq-Lin
authors: JL
authors: Yang
authors: Leslie K
authors: LK
authors: Ferrarelli
authors: Jingyan
authors: J
authors: Tian
authors: Takashi
authors: T
authors: Tadokoro
authors: Avanti
authors: A
authors: Kulkarni
authors: Lior
authors: L
authors: Weissman
authors: Guido
authors: G
authors: Keijzers
authors: David M
authors: DM
authors: Wilson
authors: Mark P
authors: MP
authors: Mattson
authors: Vilhelm A
authors: VA
authors: Bohr
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism / Q000502:physiology*; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000502:physiology*
chemical_list: D004247:DNA; D006861:Hydrogen Peroxide
references: Neurobiol Aging. 2009 Dec;30(12):2080-1
references: 18378358
references: Mol Cell Biol. 1995 Jul;15(7):3731-7
references: 7791780
references: J Biol Chem. 2010 Sep 3;285(36):28191-9
references: 20573957
references: EMBO J. 1998 Apr 15;17(8):2412-25
references: 9545252
references: J Biol Chem. 1991 Nov 15;266(32):21821-6
references: 1939206
references: Mech Ageing Dev. 2012 Apr;133(4):169-75
references: 22138376
references: Neuron. 2004 Feb 19;41(4):549-61
references: 14980204
references: J Neurochem. 2008 Nov;107(3):734-44
references: 18752643
references: Mol Cell Biol. 1988 Sep;8(9):3964-8
references: 3146694
references: DNA Repair (Amst). 2007 Jun 1;6(6):723-32
references: 17236821
references: J Biol Chem. 1996 Apr 19;271(16):9573-8
references: 8621631
references: J Cereb Blood Flow Metab. 2011 Feb;31(2):680-92
references: 20736962
references: Biochem J. 1997 Jul 1;325 ( Pt 1):1-16
references: 9224623
references: Mutat Res. 2010 Aug 14;701(1):86-91
references: 20298805
references: Mol Biol Cell. 1997 Jun;8(6):1129-42
references: 9201721
references: J Neuropathol Exp Neurol. 2008 May;67(5):377-87
references: 18431258
references: Nucleic Acids Res. 2007;35(16):5545-55
references: 17704129
references: Nature. 2011 Mar 10;471(7337):240-4
references: 21390131
references: Biotechniques. 1999 Feb;26(2):282-3, 286-9
references: 10023540
references: Free Radic Biol Med. 2008 Apr 15;44(8):1493-505
references: 18258207
references: Biochemistry. 2004 Oct 12;43(40):12924-30
references: 15461465
references: Nucleic Acids Res. 2008 Sep;36(15):5111-21
references: 18682529
references: Nucleic Acids Res. 1992 Dec 11;20(23):6209-14
references: 1475182
references: Nucleic Acids Res. 2010 May;38(9):2878-90
references: 20071746
references: Biochem Pharmacol. 1996 Mar 8;51(5):717-21
references: 8615910
references: J Neurosci Res. 2007 Apr;85(5):919-34
references: 17279544
references: DNA Repair (Amst). 2008 Jul 1;7(7):1110-20
references: 18463003
references: FEBS Lett. 1982 Jan 25;137(2):193-5
references: 7060730
references: Neuroscience. 2007 Apr 14;145(4):1233-48
references: 17303344
references: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17010-5
references: 17940040
references: J Cell Sci. 2002 Apr 1;115(Pt 7):1551-61
references: 11896201
references: Cell. 2001 Jan 12;104(1):107-17
references: 11163244
references: Mech Ageing Dev. 2008 Jul-Aug;129(7-8):475-82
references: 18374390
references: Nucleic Acids Res. 2007;35(11):3797-809
references: 17519253
references: J Biol Chem. 2005 Jun 10;280(23):22029-35
references: 15811850
references: Free Radic Res. 2005 Apr;39(4):383-8
references: 16028363
references: Nucleic Acids Res. 1998 Mar 15;26(6):1449-57
references: 9490791